ApoB DEGRADING COMPOUNDS AND USES THEREOF

Abstract

This invention provides apoB degrading compounds, compositions, methods for the treatment of cardiovascular disease and methods of manufacture. The apoB degrading compound has an asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an ApoB Binding Ligand through a Linker for the degradation of apoB and / or an atherogenic lipoprotein such as LDL, lipoprotein(a), or a triglyceride rich lipoprotein.

Description

[0001] APOB DEGRADING COMPOUNDS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No.63 / 547,325, filed November 3, 2023. The entirety of this application is hereby incorporated by reference for all purposes. FIELD OF THE INVENTION This invention provides compounds, compositions, and methods for the treatment of disorders mediated by atherogenic lipoproteins, including LDL. The compounds have an asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an Apolipoprotein B Binding Ligand through a Linker for the selective degradation of atherogenic lipoproteins to treat disorders mediated by lipoproteins. INCORPORATION BY REFERENCE The contents of the XML file named “19121-035WO1_ST26.xml” which was created on October 29, 2024, and is 167 KB in size, are hereby incorporated by reference in their entirety. BACKGROUND OF THE INVENTION Cardiovascular disease (CVD) is the leading cause of death worldwide, causing about 18 million deaths each year (World Health Organization). The two most common clinical manifestations of CVD are heart disease and stroke. A major cause of CVD is atherosclerosis, or buildup of fibrous plaques on the walls of arteries. These plaques are comprised of excess fat, cholesterol, and collagen. Lipoprotein particles are used to transport hydrophobic molecules, such as fats and cholesterol through the bloodstream to tissues around the body. These particles have an outer shell composed of phospholipids with a hydrophobic core that contains the cargo. The structure of the lipoprotein particle is organized by apolipoproteins such as apolipoprotein A (apoA) or apolipoprotein B (apoB). High-density lipoproteins (HDL), sometimes referred to as “good cholesterol”, carries fats, cholesterol, and cholesteryl esters from the cells and arterial walls back to the liver for metabolism and reutilization. Each particle of HDL is organized by 1-3 apoA protein molecules. These apoA containing particles scavenge the fats and cholesterol, thereby slowing the development of atherosclerosis and CVD. In contrast, the atherogenic lipoproteins are organized by apoB, in particular the apoB isoform apoB100. Atherogenic lipoproteins include very-low-density lipoprotein (VLDL), intermediate density lipoprotein, and low-density lipoprotein (LDL). These lipoproteins which comprise apoB are sometimes referred to as “bad cholesterol”. Each atherogenic lipoprotein particle has one apoB molecule, which serves two main roles. ApoB is a structural protein that maintains the integrity of the particle, as well as a recognition moiety for the LDL receptors on cells. ApoB, as well as atherogenic lipoproteins comprising apoB, are recognized by LDL receptors (LDLR), predominantly in the liver. Binding of the atherogenic lipoprotein to the LDLR through apoB induces endocytosis of the receptor bound to the lipoprotein particle (Brown, M. et al. “A receptor mediated pathway for cholesterol homeostasis”, Science 1986, 232(4746), 34-47). Following endocytosis, the endosome pH decreases which results in dissociation of the receptor from the lipoprotein. The lipoprotein particle is then degraded in the endosome and the LDLR is recycled to the cell surface. Mutations in the LDLR gene, impairing the number of receptors or their function, are relatively common (1 in 500 people) and are responsible for 80-85% of familial hypercholesterolemia (Heath, K. et al. “Low-density lipoprotein receptor gene (LDLR) world- wide website in familial hypercholesterolemia: update, new features, and mutation analysis” 2001, Atherosclerosis, 154(1), 243-246; Benito-Vicente, A. et al. “Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease” 2018, Int. J. Mol. Sci, 19). If untreated, familial hypercholesterolemia significantly increases the risk of CVD, heart attack and stroke. LDLR mutations are classified according to their phenotype as: class 1 (no protein synthesis), class 2 (partial or complete retention of LDLR in the endoplasmic reticulum), class 3 (defective binding to apoB), class 4 (defective endocytosis), and class 5 (diminished LDLR recycling capacity) (“Familial Hypercholesterolima: Genes and Beyond”, NCBI Bookshelf, adapted from Gidding, SS. et al. Circulation 2015; 132:2167-2192). Despite significant research into methods to decrease the levels of atherogenic lipoproteins, sometimes referred to as “high cholesterol”, CVD still claims nearly 18 million lives per year. HMG-CoA reductase inhibitors (“statins”), such as atorvastatin (Lipitor®), have been used to reduce LDL levels in many patients. However, response to statin therapy is variable, with patients experiencing 5-70% reduction in LDL levels even when the patient can tolerate a therapeutically effective dose (Reiner, Z. “Resistance and intolerance to statins” Nutrition, Metabolism, and Cardiovascular Diseases, 2014, 24(10), 1057-1066). Statins can cause significant side effects including muscle pain, liver damage, high blood sugar and memory loss, which may result in decreasing the dosage or discontinuation of therapy altogether (Mayo Clinic “Statin Side Effects” updated May 27, 2023). Another class of therapeutics to treat high cholesterol are PCSK9 inhibitors. These antibody-based therapeutics have been shown to decrease cholesterol levels in patients, but like statins, concerns have been raised by the U.S. Food and Drug Administration that they may cause neurocognitive impairment. Other atherogenic lipoproteins, including lipoprotein(a) and triglyceride rich lipoproteins are established risk factors for CVD. Lipoprotein(a) is a variant of LDL which comprises apoB and apoA. However, LDL-lowering strategies such as statins and PCSK9 therapies are unable to manage lipoprotein(a) and triglyceride rich lipoprotein levels. Microsomal triglyceride transfer protein (MTP) is a chaperone protein that assists in loading nascent LDL particles with fats and cholesterol. MTP has 100% sequence homology probability with residues 43-1017 of apoB (Keiran, K. et al. “A New Structural Model of Apolipoprotein B100 Based on Computational Modeling and Cross Linking” Int. J. Mol. Sci. 2022, 23, 11480). However, inhibition of MTP, and thus formation of LDL particles, causes lipid accumulation within hepatocytes resulting in hepatic steatosis. While some progress has been made in the field of treating cardiovascular diseases, there remains a need for additional strategies to combat the leading cause of death worldwide. SUMMARY OF THE INVENTION ApoB degrading compounds and their pharmaceutically acceptable salts and compositions thereof and their methods of use and manufacture are provided. The compounds of the present invention contain an ASGPR Binding Ligand covalently attached by a Linker to an apoB Binding Ligand. The ASGPR Binding Ligands used in the compounds described herein include derivatives of six-carbon pyranose moieties, specifically galactose and talose. These two sugars, shown below, differ only in the stereochemistry of the C2substituent. The “down” C2configuration corresponds to the stereochemistry of galactose, while the C2substituent in the “up” configuration corresponds to the stereochemistry of talose. In certain embodiments the ASGPR Binding Ligand of the compound of the present invention is in the galactose stereochemistry configuration. It has been disco escribed herein can be used to bind the asialoglycoprotein receptor with high affinity, facilitating improved degradation. In certain aspects of the invention, the apoB degrading compounds degrade atherogenic lipoproteins comprising apoB. In certain embodiments the atherogenic lipoprotein that is degraded is low density lipoprotein (LDL), intermediate density lipoprotein (IDL), very low-density lipoprotein (VLDL), lipoprotein(a) (Lp (a)), triglyceride rich lipoproteins (TRLs), or a combination thereof. In certain embodiments, the apoB degrading compounds degrade LDL, Lp (a), and TRLs. In certain aspects of the invention, the apoB degrading compound of the present invention can be used to decrease levels of atherogenic lipoproteins in patients who have familial hypercholesterolemia. LDL and other atherogenic lipoproteins are degraded through LDLR- mediated endocytosis. However, 1 in 500 people have an LDLR mutation which impairs this natural process. In certain embodiments the apoB degrading compound of the present invention can be used to decrease levels of atherogenic lipoproteins in patients who are resistant to statins or are statin intolerant. In certain aspects an apoB degrading compound of Formula I, Formula II, or Formula III is provided: (I) ) I); or a pharma wherein ASGPR Binding Ligand is a compound selected from:

[0002] ; in certain embodiments Q is -O-; in certain embodiments Q is -N(R10)-; in certain embodiments Q is -NH-; R1and R5are independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, halogen, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-cyano, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0- C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3, C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, or C0-C6alkyl-O-S(O)2R3; in certain embodiments R1is hydrogen; R3at each occurrence is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, -OR8, and -NR8R9; R6and R7are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R8and R9are independently selected at each occurrence from hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocycle; R10is hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, C(O)R3, S(O)R3, C(S)R3, or S(O)2R3; in certain embodiments R10is hydrogen; R65, R66, and R67are independently selected at each occurrence from the group consisting of hydrogen, C0-C6alkyl-cyano, alkyl, alkenyl, alkynyl, haloalkyl, F, Cl, Br, I, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl- C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, and C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from R80; R80is independently selected at each instance from the group consisting of alkyl (including C1-C4alkyl), alkenyl (including C2-C4alkenyl), alkynyl (including C2-C4alkynyl), haloalkyl (including C1-C4haloalkyl), -OR6, F, Cl, Br, I, -NR6R7, heterocycle, heteroaryl, aryl, cyano, nitro, hydroxyl, azide, amide, -SR6, -S(O)(NR6)R3, -NR8C(O)R3, -C(O)NR6R7, and -C(O)R3; LinkerAis a bond or a moiety that covalently links LinkerB, LinkerC, or LinkerDto the ASGPR Binding Ligand; LinkerBis a bond or a moiety that covalently links LinkerAto the ApoB Binding Ligand; LinkerCis a chemical group that links each LinkerAto the ApoB Binding Ligand; LinkerDis a chemical group that links each LinkerAto the ApoB Binding Ligand; and ApoB Binding Ligand is a ligand that binds to apolipoprotein B. In another aspect the ASGPR Binding Ligand for use in a compound of Formula I, Formula II, or Formula III is a compound selected from: ; wherein: Q2is selected from -O-, -N(R10)-, S, S(O), C(R4a)(R4b), and S(O)2; L is selected from and ; is heteroar y or p eny , eac o w c s optionally substituted with 1 or 2 substituents independently selected from R65; R4ais selected from hydrogen, alkyl, haloalkyl, and halogen; and R4bis selected from hydrogen, alkyl, haloalkyl, halogen, C0-C6alkyl-OR6, C0-C6alkyl-SR6, and C0-C6alkyl-NR6R7. In another aspect the ASGPR Binding Ligand for use in a compound of Formula I, Formula II, or Formula III is a compound selected from: ; 48b , N(R48a)-C(O)- N(R48b)(R48c), N(R48a)-C(O)-OR48b, N(R48a)-S(O)2-R48b, tetrazole, or triazole, wherein the tetrazole and triazole are optionally substituted with one R48asubstituent; R48a, R48b, and R48care each independently selected from H, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkenyl, C1-C6alkynyl, C2-C6haloalkenyl, and C2-C6haloalkynyl, wherein one or two - CH2- groups of the alkyl may be replaced with a heteroatom group independently selected from - O-, -S-, and -N(R52a)- and wherein one or two -CH3 groups of the alkyl may be independently replaced with a heteroatom group selected from -N(R52a)(R52a), -OR52a, and -SR52awherein the heteroatom groups are separated by at least 2 carbon atoms; R52ais independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkenyl, C1-C6 alkynyl, C2-C6haloalkenyl, and C2-C6haloalkynyl. In certain embodiments the ASGPR Binding Ligand is selected from: . In non-limiting embodiments, LinkerAand LinkerBare independently selected from: ; LinkerCis select nd LinkerDis sel ; wherein: R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are independently at each occurrence selected from the group consisting of a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO2-, -S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, -P(O)(R3)O-, -P(O)(R3)-, a divalent residue of a natural or unnatural amino acid, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, -CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O- (CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, -[C(O)-CH2-O]n-, a divalent residue of a fatty acid, and a divalent residue of an unsaturated or saturated mono- or di-carboxylic acid; each of which is optionally substituted with 1, 2, or 3 substituents independently selected from R21; n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, hydroxyl, alkoxy, azide, amino, cyano, -NR6R7, -NR8SO2R3, -NR8S(O)R3, haloalkyl, aryl, heteroaryl, and heterocycle; R22is independently at each occurrence selected from the group consisting of alkyl, -C(O)N-, -NC(O)-, -N-, -C(R21)-, -P(O)O-, -P(O)-, -P(O)(NR6R7)N-, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from R21; R32is independently at each occurrence selected from the group consisting of alkyl, N+X-, -C-, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from R21; X- is an anionic group, for example Br- or Cl-; and all other variables are as defined herein. In certain embodiments LinkerAis bond and LinkerBis . In certain em . In certain em g g p elected from: In ce . In other embo .

[0003] In certain embodiments the compound of the present invention is of Formula: ; wherein n is 0, 1, 2, 3, 4, 5, 6,7, 8, 9, or 10; and . In other embodiments the compound of the present invention is of Formula: , ,

[0004] , , In certain embodiments, the compound of the present invention is of Formula

[0005] p y p . In certain embodiments, the apoB degrading compound is selected from

[0006] , tion feature select ASGPR ligands that provide high binding affinity for ASGPR. As a result of this high ASGPR binding affinity, these compounds may be administered in lower doses, have fewer side effects, decreased side effects, increased efficacy, faster therapeutic effect, longer metabolic stability, and / or longer therapeutic benefit than conventional cholesterol lowering compounds. A compound of the present invention can be particularly beneficial in the treatment of a patient with decreased LDLR function. In certain embodiments, the compounds of the present invention are used to treat a patient with an LDLR mutation. In certain embodiments, the compounds of the present invention are used to treat a patient with a class 1, class 2, class 3, class 4, or class 5 LDLR mutation. A compound of the present invention can also be beneficial in the treatment of a patient with high cholesterol and who is statin resistant or statin intolerant. In certain embodiments the patient is statin resistant. In certain embodiments the patient is statin intolerant. In certain embodiments the compound of the present invention is provided as an isotopically enriched compound, for example a compound with at least one desired isotopic substitution of an atom, at an amount above the natural abundance of the isotope. For example, deuterium can replace one or more hydrogens and13C can replace one or more carbon atoms. In one embodiment, the isotopic substitution is in one or more positions of the ASGPR Binding Ligand. In another embodiment, the isotopic substitution is in one or more positions of the Linker portion of the molecule (LinkerA, LinkerB, LinkerC, or LinkerD). In another embodiment, the isotopic substitution is in one or more positions of the ApoB Binding Ligand portion of the molecule. The present invention thus includes at least the following features: (i) An apoB degrading compound described herein or a pharmaceutically acceptable salt thereof; (ii) Use of an apoB degrading compound described herein or a pharmaceutically acceptable salt thereof, in treating a medical disorder, for example high cholesterol; (iii) An isotopically enriched derivative of an apoB degrading compound described herein or a pharmaceutically acceptable salt thereof; (iv) A process for manufacturing a medicament intended for the therapeutic use for treating or preventing a disorder, characterized in that an apoB degrading compound described herein or a pharmaceutically acceptable salt thereof is used in the manufacture; (v) An apoB degrading compound described herein or a pharmaceutically acceptable salt thereof in a purified or substantially pure form (e.g., at least 90, 95, 96, 97, 98, 99, 99.5, or 99.9%); (vi) An apoB degrading compound described herein or a pharmaceutically acceptable salt thereof to treat a disorder described herein; and (vii) A method for the manufacture of an apoB degrading compound described herein. BRIEF DESCRIPTION OF THE FIGURES FIG.1 is an image of HepG2 cells stained with nuclear dye Hoechst (Example 5). The cells were treated with apoB degrading compounds of the present invention, estradiol or T1AM. Lovastatin was used as the positive control. The image in FIG. 1 was taken at 24 hours after treatment. FIG. 2 shows a timecourse study of LDL uptake in HepG2 cells treated with the apoB degrading compounds of the present invention (Example 5). Lovastatin was used as a positive control. The samples treated with either Compound 1 or Compound 3 induced higher uptake than cells treated with lovastatin. The combination of lovastatin and either Compound 1 or Compound 3 resulted in the highest uptake levels. FIG.3 shows a boxplot representing percent increase in LDL uptake by HepG2 cells treated with apoB degrading compounds of the present invention (Example 5). Each box represents the data from 8 replicates per group. The samples treated with either Compound 1 (60% higher uptake than control) or Compound 3 (55% higher uptake than control) induced significantly higher uptake than cells treated with lovastatin (44% higher uptake than control, p<0.0001). The combination of lovastatin and either Compound 1 or Compound 3 resulted in the highest uptake levels (70% and 68%, respectively). FIG. 4 shows the degradation of LDL in mice after injection of Compound 1. LDL was introduced to LDL receptor knockout mice followed by administration of Compound 3 or vehicle (Example 6). Plasma LDL levels in mice administered Compound 3 were lower than those administered vehicle control. The lower LDL levels in treated mice confirm that Compound 3 induces uptake and degradation of LDL through ASGPR-mediated endocytosis. DETAILED DESCRIPTION OF THE INVENTION Compounds and their pharmaceutically acceptable salts and compositions thereof that degrade apoB, as well as starting materials and intermediates for such compounds and their methods of use and manufacture are provided. These apoB degrading compounds are highly potent binders of ASGPR and apoB. In certain embodiments the apoB degrading compound binds to apoB and is carried to the liver where it binds to ASGPR, inducing endocytosis and degradation of apoB. In some embodiments, apoB is part of a lipoprotein particle, including but not limited to an LDL particle. In some embodiments, an apoB degrading compound that incorporates one of the high binding ASGPR ligands as described herein can be sufficiently active in the form of a monodentate compound (i.e., 1:1 ratio of ApoB Binding Ligand to ASGPR ligand in the therapeutic molecule). The asialoglycoprotein receptor (ASGPR) is a Ca2+-dependent lectin that is primarily expressed in parenchymal hepatocyte cells. The main role of ASGPR is to help regulate serum glycoprotein levels by mediating endocytosis of desialylated glycoproteins. The receptor binds ligands with a terminal galactose or N-acetylgalactosamine. Asialoglycoproteins bind to ASGPRs and are then cleared by receptor-mediated endocytosis. The receptor and the protein are dissociated in the acidic endosomal compartment and the protein is eventually degraded by lysosomes. Heterobifunctional compounds have been developed that use an ASGPR ligand to degrade an extracellular protein. Publications describing various ASGPR ligands include: U.S. Patent Nos. 9,340,553; 9,617,293; 10,039,778; 10,376,531, and 10,813,942 assigned to Pfizer Inc.; Sanhueza et al. (JACS, 2017, 139, 3528); Petrov et al. (Bioorganic and Medicinal Chemistry Letters, 2018, 28, 382); WO 2018 / 223073 and WO2018 / 223081 assigned to Pfizer Inc. and Wave Life Sciences Ltd.; WO 2018 / 223056 assigned to Wave Sciences Ltd.; Schmidt et al. (Nucleic Acids Research, 2017, 45, 2294); Huang et al. (Bioconjugate Chem. 2017, 28, 283); WO 2019 / 199621, WO 2019 / 199634; WO 2020 / 132100 assigned to The Board of Trustees of the Leland Stanford Junior University; WO 2021 / 072246, WO 2021 / 072269, WO 2021 / 142377 assigned to Lycia Therapeutics; Banik et al. (Nature, 2020, 584, 291); WO 2022 / 192478, WO 2022 / 178425 assigned to Yale University; WO 2022 / 084331 assigned to Sanofi; WO2022 / 192478 assigned to Biohaven Therapeutics; an article from the Bertozzi group titled “LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation,” (Ahn, et al. Nat. Chem. Biol. (2021)) published in the journal Nature Chemical Biology; and WO 2021 / 155317, WO 2022 / 035997, WO 2022 / 235699, WO2023 / 009554, and WO 2023 / 028338 assigned to Avilar Therapeutics Inc. Examples of publications describing the use of apoB degraders for the treatment of hyperlipidemia include WO 2009 / 041037 and EP 2,191,849 assigned to Kowa Ltd.; WO 2021 / 156792 and WO 2022 / 157626 assigned to Novartis; and WO 2023 / 288033 assigned to Lycia Therapeutics. I. DEFINITIONS Compounds are described using standard nomenclature. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. The compounds described herein include independently the enantiomers, mixtures of enantiomers, diastereomers, tautomers, racemates and other isomers, as if each is specifically described, unless otherwise indicated or otherwise excluded by context. The terms “a” and “an” do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced item. The term “or” means “and / or”. Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The endpoints of all ranges are included within the range and independently combinable. All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of examples, or exemplary language (e.g., “such as”), is intended merely to better illustrate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. Unless defined otherwise, technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. The present invention includes compounds with at least one desired isotopic substitution of an atom, at an amount above the natural abundance of the isotope, i.e., enriched. Examples of isotopes that can be incorporated into compounds, of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, and chlorine, such as2H,3H,11C,13C,14C,15N,17O,18O,18F31P,32P,35S,36Cl, and125I respectively. In one embodiment, isotopically labeled compounds can be used in metabolic studies (with, for example14C), reaction kinetic studies (with, for example2H or3H), detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays, or in radioactive treatment of patients. Isotopically labeled compounds of this invention and prodrugs thereof can generally be prepared by carrying out the procedures disclosed in the schemes or in the examples and preparations described below by using a readily available isotopically labeled reagent instead of a non-isotopically labeled reagent. By way of general example and without limitation, isotopes of hydrogen, for example, deuterium (2H) and tritium (3H) may optionally be used anywhere in described structures that achieves the desired result. Alternatively, or in addition, isotopes of carbon, e.g.,13C and14C, may be used. In one embodiment, the isotopic substitution is accomplished by replacing hydrogen with a deuterium at one or more locations on the molecule to improve the performance of the drug, for example, the pharmacodynamics, pharmacokinetics, biodistribution, half-life, stability, AUC, Tmax, Cmax, etc. For example, the deuterium can be bound to carbon in a location of bond breakage during metabolism (an α-deuterium kinetic isotope effect) or next to or near the site of bond breakage (a β-deuterium kinetic isotope effect). Isotopic substitutions, for example deuterium substitutions, is typically partial. Partial isotopic substitution means that at least one hydrogen is substituted with deuterium. In certain embodiments, the isotope is 80, 85, 90, 95 or 99% or more enriched in an isotope at any location of interest. In certain embodiments deuterium is 80, 85, 90, 95 or 99% enriched at a desired location. Unless otherwise stated, the enrichment at any point is above natural abundance, and in certain nonlimiting embodiments is enough to alter a detectable property of the drug in a human. A “dosage form” means a unit of administration of an active agent. Examples of dosage forms include intravenous formulations, solid dosage forms, tablets, capsules, injections, suspensions, liquids, emulsions, implants, particles, spheres, creams, ointments, suppositories, inhalable forms, transdermal forms, buccal, sublingual, parenteral, systemic, topical, gel, mucosal, implant, and the like. “Pharmaceutical compositions” are compositions comprising at least one active agent, and at least one other pharmaceutically acceptable substance, such as a carrier. The present invention includes pharmaceutical compositions of the apoB degrading compounds. “Pharmaceutical combinations” are combinations of at least two active agents which may be combined in a single dosage form or provided together in separate dosage forms. A “pharmaceutically acceptable salt” is a derivative of the disclosed compound wherein the parent molecule is modified by making inorganic and organic, pharmaceutically acceptable, acid or base addition salts thereof. The salt of an apoB degrading compound can be synthesized by reaction of a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting free acid forms of an apoB degrading compound with a stoichiometric amount of the appropriate base (such as Na, Ca, Mg, or K hydroxide, carbonate, bicarbonate, or the like), or by reacting free base forms of apoB degrading compounds with a stoichiometric amount of the appropriate acid. Such reactions are typically carried out in water or in an organic solvent, or in a mixture of the two. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include salts which are acceptable for human consumption. Examples, of such salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, mesylic, esylic, besylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, HOOC-(CH2)1-4-COOH, and the like, or using an acid that produces the same counterion. Lists of additional suitable salts may be found, e.g., in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., p.1418 (1985). In certain non-limiting embodiments, the invention includes a prodrug form of a compound described herein. The term “prodrug” refers to a compound which when administered to a host in vivo is converted into a compound of the present invention (the “parent drug”). A prodrug can be used to achieve a desired effect, including for example to improve a chemical or pharmacokinetic property of the parent drug. In certain embodiments the prodrug is an amide, ester, ether, phosphate, phosphonate, sulfonyl, or anhydride version of a compound of the present invention. The prodrug can be formed by covalently attaching a removable group to the compound of the present invention. Non-limiting examples of reactions to introduce removable groups include acylation, phosphorylation, phosphonylation, phosphoramidation, amidation, esterification, and carbonylation. The term “carrier” applied to pharmaceutical compositions / combinations of the invention refers to a pharmaceutically acceptable diluent, excipient, or vehicle with which an active compound is provided. A “pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition / combination that is generally safe, acceptable for human consumption, and neither biologically nor otherwise inappropriate for administration to a host, typically a human. In one embodiment, an excipient is used that is acceptable for veterinary use. A “patient” or “host” or “subject” is a human or non-human animal in need of treatment or prevention of any of the disorders as specifically described herein. Typically, the host, patient, or subject is a human. A “patient” or “host” or “subject” may in certain embodiments where warranted include a veterinary application, for example, to a mammal, primate (e.g., human), horse, dog, cat, cow, sheep, goat, and the like. In one embodiment, the substitution of a hydrogen atom for a deuterium atom occurs within any variable group. For example, when any variable group is, or contain for example through substitution, methyl, ethyl, or methoxy, the alkyl residue may be deuterated (in nonlimiting embodiments, CDH2, CD2H, CD3, CD2CD3, CHDCH2D, CH2CD3, CHDCHD2, OCDH2, OCD2H, or OCD3 etc.). The term “atherogenic lipoprotein” as used herein refers to a lipoprotein that comprise at least one apoB protein and is associated with cardiovascular disease. Non-limiting examples of atherogenic lipoproteins include intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), lipoprotein(a), triglyceride rich lipoproteins, and chylomicrons (sometimes referred to as ultra low-density lipoprotein ULDL). The term “polypeptide” as used herein, refers to any polymeric chain of amino acids. The terms “peptide” and “protein” are used interchangeably with the term polypeptide and also refer to a polymeric chain of amino acids. The term “polypeptide” encompasses native or artificial proteins, protein fragments, and polypeptide analogs of a protein sequence. A polypeptide may be monomeric or polymeric. A dash ("-") that is not between two letters or symbols is used to indicate a point of attachment for a substituent. For example, -(C=O)NH2is attached through carbon of the keto (C=O) group. The term “substituted”, as used herein, means that any one or more hydrogens on the designated atom or group is replaced with a moiety selected from the indicated group, provided that the designated atom's normal valence is not exceeded and the resulting compound is stable. For example, when the substituent is oxo (i.e., =O) then two hydrogens on the atom are replaced. For example, a pyridyl group substituted by oxo is a pyridone. Combinations of substituents and / or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates. “Alkyl” is a branched, straight chain, or cyclic saturated aliphatic hydrocarbon group. Unless denoted otherwise, “alkyl” is typically C1-C12alkyl. In certain embodiments the alkyl contains from 1 to about 12 carbon atoms, more generally from 1 to about 6 carbon atoms, from 1 to about 4 carbon atoms, or from 1 to 3 carbon atoms. In one embodiment, the alkyl contains from 1 to about 8 carbon atoms. In certain embodiments, the alkyl is C1-C2, C1-C3, C1-C4, C1-C5 or C1- C6.The specified ranges as used herein indicate an alkyl group which is considered to explicitly disclose as individual species each member of the range described as a unique species. For example, the term C1-C6 alkyl as used herein indicates a straight or branched alkyl group having from 1, 2, 3, 4, 5, or 6 carbon atoms and also a carbocyclic alkyl group of 3, 4, 5, or 6 carbon atoms and is intended to mean that each of these is described as an independent species. For example, the term C1-C4alkyl as used herein indicates a straight or branched alkyl group having from 1, 2, 3, or 4 carbon atoms and is intended to mean that each of these is described as an independent species. When C0-Cnalkyl is used herein in conjunction with another group, for example, (C3-C7cycloalkyl)C0-C4 alkyl, or –C0-C4alkyl(C3-C7cycloalkyl), the indicated group, in this case cycloalkyl, is either directly bound by a single covalent bond (C0alkyl), or attached by an alkyl chain in this case 1, 2, 3, or 4 carbon atoms. Alkyls can also be attached via other groups such as heteroatoms as in –O-C0-C4alkyl(C3-C7cycloalkyl). Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, tert- pentyl, neopentyl, n-hexyl, 2-methylpentane, 3-methylpentane, 2,2-dimethylbutane, 2,3- dimethylbutane, and hexyl. When a term is used that includes “alk” it should be understood that “cycloalkyl” or “carbocyclic” can be considered part of the definition, unless unambiguously excluded by the context. For example, and without limitation, the terms alkyl, alkenyl, alkynyl, alkoxy, alkanoyl, alkenloxy, haloalkyl, etc. can all be considered to include the cyclic forms of alkyl, unless unambiguously excluded by context. “Alkenyl” is a branched or straight chain aliphatic hydrocarbon group having one or more carbon-carbon double bonds that may occur at a stable point along the chain. Unless denoted otherwise, “alkenyl” is typically C2-C12 alkenyl. Nonlimiting examples are C2-C8alkenyl, C2- C7alkenyl, C2-C6alkenyl, C2-C5alkenyl and C2-C4alkenyl. The specified ranges as used herein indicate an alkenyl group having each member of the range described as an independent species, as described above for the alkyl moiety. Examples of alkenyl include, but are not limited to, ethenyl and propenyl. “Alkynyl” is a branched or straight chain aliphatic hydrocarbon group having one or more carbon-carbon triple bonds that may occur at any stable point along the chain. Unless denoted otherwise, “alkynyl” is typically C2-C12 alkynyl. In certain embodiments alkynyl is C2-C8alkynyl or C2-C6alkynyl. The specified ranges as used herein indicate an alkynyl group having each member of the range described as an independent species, as described above for the alkyl moiety. Examples of alkynyl include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, 3- butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4- hexynyl and 5-hexynyl. “Alkoxy” is an alkyl group as defined above covalently bound through an oxygen bridge (-O-). Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, 2-butoxy, t-butoxy, n-pentoxy, 2-pentoxy, 3-pentoxy, isopentoxy, neopentoxy, n- hexoxy, 2-hexoxy, 3-hexoxy, and 3-methylpentoxy. Similarly, an “alkylthio” or a “thioalkyl” group is an alkyl group as defined above with the indicated number of carbon atoms covalently bound through a sulfur bridge (-S-). In one embodiment, the alkoxy group is optionally substituted as described above. “Haloalkyl” indicates both branched and straight-chain alkyl groups substituted with 1 or more halogen atoms, up to the maximum allowable number of halogen atoms. Examples of haloalkyl include, but are not limited to, trifluoromethyl, monofluoromethyl, difluoromethyl, 2- fluoroethyl, and penta-fluoroethyl. In certain embodiments, haloalkyl is branched and straight- chain alkyl groups substituted with 1 or more halogen atoms selected independently at each instance from chlorine and fluorine, up to the maximum allowable number of halogen atoms. In certain embodiments, the haloalkyl is a fluoroalkyl. In certain embodiments, the haloalkyl is a chloroalkyl. “Aryl" indicates an aromatic group containing only carbon in the aromatic ring or rings. In one embodiment, the aryl group contains 1 to 3 separate or fused rings and is 6 to 14 or 18 ring atoms, without heteroatoms as ring members. The term “aryl” includes groups where a saturated or partially unsaturated carbocycle group is fused with an aromatic ring. The term “aryl” also includes groups where a saturated or partially unsaturated heterocycle group is fused with an aromatic ring so long as the attachment point is the aromatic ring. Such compounds may include aryl rings fused to a 4 to 7 or a 5 to 7-membered saturated or partially unsaturated cyclic group that optionally contains 1, 2 or 3 heteroatoms independently selected from N, O, B, P, Si and S, to form, for example, a 3,4-methylenedioxyphenyl group. Aryl groups include, for example, phenyl and naphthyl, including 1-naphthyl and 2-naphthyl. In one embodiment, aryl groups are pendant. An example of a pendant ring is a phenyl group substituted with a phenyl group. The term “heterocycle” refers to saturated and partially saturated heteroatom-containing ring radicals, where the heteroatoms may be selected from N, S, and O. The term “heterocycle” includes monocyclic 3-12 membered rings, as well as bicyclic 5-16 membered ring systems (which can include fused, bridged, or spiro, bicyclic ring systems). It does not include rings containing - O-O- or -S-S- portions. Examples of saturated heterocycle groups include saturated 4- to 7- membered monocyclic groups containing 1 to 4 nitrogen atoms [e.g., pyrrolidinyl, imidazolidinyl, piperidinyl, pyrrolinyl, azetidinyl, piperazinyl, and pyrazolidinyl]; saturated 4 to 6-membered monocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g., morpholinyl]; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., thiazolidinyl]. Examples of partially saturated heterocycle radicals include but are not limited to, dihydrothienyl, dihydropyranyl, dihydrofuryl, and dihydrothiazolyl. Examples of partially saturated and saturated heterocycle groups include but are not limited to, pyrrolidinyl, imidazolidinyl, piperidinyl, pyrrolinyl, pyrazolidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, thiazolidinyl, dihydrothienyl, 2,3-dihydro-benzo[l,4]dioxanyl, indolinyl, isoindolinyl, dihydrobenzothienyl, dihydrobenzofuryl, isochromanyl, chromanyl, 1,2- dihydroquinolyl, 1,2,3,4- tetrahydro-isoquinolyl, 1 ,2,3,4-tetrahydro-quinolyl, 2,3,4,4a,9,9a- hexahydro-lH-3-aza-fluorenyl, 5,6,7- trihydro-l,2,4-triazolo[3,4-a]isoquinolyl, 3,4-dihydro-2H- benzo[l,4]oxazinyl, benzo[l,4]dioxanyl, 2,3- dihydro-lH-lλ’-benzo[d]isothiazol-6-yl, dihydropyranyl, dihydrofuryl and dihydrothiazolyl. “Bicyclic heterocycle” includes groups wherein the heterocyclic radical is fused with an aryl radical wherein the point of attachment is the heterocycle ring. “Bicyclic heterocycle” also includes heterocyclic radicals that are fused or bridged with a carbocycle radical. For example partially unsaturated condensed heterocyclic group containing 1 to 5 nitrogen atoms, for example, indoline, isoindoline, partially unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, partially unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, and saturated condensed heterocyclic group containing 1 to 2 oxygen or sulfur atoms. Non-limiting examples of bicyclic heterocycles include: , . clear from the context, the term “bicyclic heterocycle” includes cis and trans diastereomers. Non-limiting examples of chiral bicyclic heterocycles include: . ed and partially saturated heteroatom-containing ring radicals, where the heteroatoms may be selected from N, S, O, B, Si, and P. “Heteroaryl” refers to a stable monocyclic, bicyclic, or multicyclic aromatic ring which contains from 1 to 3, or in some embodiments from 1, 2, or 3 heteroatoms selected from N, O, S, B, and P (and typically selected from N, O, and S) with remaining ring atoms being carbon, or a stable bicyclic or tricyclic system containing at least one 5, 6, or 7 membered aromatic ring which contains from 1 to 3, or in some embodiments from 1 to 2, heteroatoms selected from N, O, S, B or P with remaining ring atoms being carbon. In one embodiment, the only heteroatom is nitrogen. In one embodiment, the only heteroatom is oxygen. In one embodiment, the only heteroatom is sulfur. Monocyclic heteroaryl groups typically have from 5 or 6 ring atoms. In some embodiments bicyclic heteroaryl groups are 8- to 10-membered heteroaryl groups, that is, groups containing 8 or 10 ring atoms in which one 5, 6, or 7-member aromatic ring is fused to a second aromatic or non-aromatic ring wherein the point of attachment is the aromatic ring. When the total number of S and O atoms in the heteroaryl group exceeds 1, these heteroatoms are not adjacent to one another. In one embodiment, the total number of S and O atoms in the heteroaryl group is not more than 2. In another embodiment, the total number of S and O atoms in the aromatic heterocycle is not more than 1. Examples of heteroaryl groups include, but are not limited to, pyridinyl (including, for example, 2-hydroxypyridinyl), imidazolyl, imidazopyridinyl, pyrimidinyl (including, for example, 4-hydroxypyrimidinyl), pyrazolyl, triazolyl, pyrazinyl, furyl, thienyl, isoxazolyl, thiazolyl, oxadiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, tetrahydrofuranyl, and furopyridinyl. Heteroaryl groups are optionally substituted independently with one or more substituents described herein. “Heteroaryloxy” is a heteroaryl group as described bound to the group it substituted via an oxygen, -O-, linker. “Heteroarylalkyl” is an alkyl group as described herein substituted with a heteroaryl group as described herein. “Arylalkyl” is an alkyl group as described herein substituted with an aryl group as described herein. “Heterocycloalkyl” is an alkyl group as described herein substituted with a heterocyclo group as described herein. “Silyl” is a silicon atom substituted with three alkyl groups as described herein. Nonlimiting examples of silyl groups include: trimethylsilyl, triethylsilyl, triisopropylsilyl, tert- butyldimethylsilyl, Embodiments of “alkyl” In certain embodiments “alkyl” is a C1-C12alkyl, C1-C10alkyl, C1-C9alkyl, C1-C8alkyl, C1-C7alkyl, C1-C6alkyl, C1-C5alkyl, C1-C4alkyl, C1-C3alkyl, or C1-C2alkyl. In certain embodiments “alkyl” is a C1-C10alkyl, C1-C9alkyl, C1-C8alkyl, C1-C7alkyl, C1-C6alkyl, C1-C5alkyl, C1-C4alkyl, C1-C3alkyl, or C1-C2alkyl. In certain embodiments “alkyl” has one carbon. In certain embodiments “alkyl” has two carbons. In certain embodiments “alkyl” has three carbons. In certain embodiments “alkyl” has four carbons. In certain embodiments “alkyl” has five carbons. In certain embodiments “alkyl” has six carbons. Non-limiting examples of “alkyl” include: methyl, ethyl, propyl, butyl, pentyl, and hexyl. Additional non-limiting examples of “alkyl” include: isopropyl, isobutyl, isopentyl, and isohexyl. Additional non-limiting examples of “alkyl” include: sec-butyl, sec-pentyl, and sec-hexyl. Additional non-limiting examples of “alkyl” include: tert-butyl, tert-pentyl, and tert-hexyl. Additional non-limiting examples of “alkyl” include: neopentyl, 3-pentyl, and active pentyl. In an alternative embodiment the “alkyl” group is optionally substituted. In an alternative embodiment the “alkenyl” group is optionally substituted. In an alternative embodiment the “alkynyl” group is optionally substituted. Embodiments of “haloalkyl” In certain embodiments “haloalkyl” is a C1-C10haloalkyl, C1-C9haloalkyl, C1-C8haloalkyl, C1-C7haloalkyl, C1-C6haloalkyl, C1-C5haloalkyl, C1-C4haloalkyl, C1-C3haloalkyl, and C1- C2haloalkyl. In certain embodiments “haloalkyl” has one carbon. In certain embodiments “haloalkyl” has one carbon and one halogen. In certain embodiments “haloalkyl” has one carbon and two halogens. In certain embodiments “haloalkyl” has one carbon and three halogens. In certain embodiments “haloalkyl” has two carbons. In certain embodiments “haloalkyl” has three carbons. In certain embodiments “haloalkyl” has four carbons. In certain embodiments “haloalkyl” has five carbons. In certain embodiments “haloalkyl” has six carbons. Non-limiting examples of “haloalkyl” include: . Additional non-limiting examples of “haloalkyl” include: , . Additional non-limiting examples of “haloalkyl” include: , , and . Embodiments of “heteroaryl” Non-limiting examples of 5 membered “heteroaryl” groups include pyrrole, furan, thiophene, pyrazole, imidazole, triazole, isoxazole, oxazole, oxadiazole, oxatriazole, isothiazole, thiazole, thiadiazole, and thiatriazole. Additional non-limiting examples of 5 membered “heteroaryl” groups include: , r 3 nitrogen atoms (i.e. pyridinyl, pyridazinyl, triazinyl, pyrimidinyl, and pyrazinyl). Non-limiting examples of 6 membered “heteroaryl” groups with 1 or 2 nitrogen atoms include: , ontaining 1 or 2 atoms selected from nitrogen, oxygen, and sulfur. Non-limiting examples of “heteroaryl” groups that are bicyclic include indole, benzofuran, isoindole, indazole, benzimidazole, azaindole, azaindazole, purine, isobenzofuran, benzothiophene, benzoisoxazole, benzoisothiazole, benzooxazole, and benzothiazole. Additional non-limiting examples of “heteroaryl” groups that are bicyclic include: . : . clic include: . tic group containing 1 or 2 atoms selected from nitrogen, oxygen, and sulfur. Non-limiting examples of “heteroaryl” groups that are bicyclic include quinoline, isoquinoline, quinoxaline, phthalazine, quinazoline, cinnoline, and naphthyridine. Additional non-limiting examples of “heteroaryl” groups that are bicyclic include: . Embodiments of “heterocycle” In certain embodiments “heterocycle” refers to a cyclic ring with one nitrogen and 3, 4, 5, 6, 7, or 8 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with one nitrogen and 3, 4, or 5 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with one nitrogen and one oxygen and 3, 4, 5, 6, 7, or 8 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with one nitrogen and one oxygen and 4, 5, or 6 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with two nitrogens and 3, 4, 5, 6, 7, or 8 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with two nitrogens and 4, 5, or 6 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with one oxygen and 3, 4, 5, 6, 7, or 8 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with one oxygen and 3, 4, or 5 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with one sulfur and 3, 4, 5, 6, 7, or 8 carbon atoms. In certain embodiments “heterocycle” refers to a cyclic ring with one sulfur and 3, 4, or 5 carbon atoms. Non-limiting examples of “heterocycle” include aziridine, oxirane, thiirane, azetidine, 1,3- diazetidine, oxetane, and thietane. Additional non-limiting examples of “heterocycle” include pyrrolidine, 3-pyrroline, 2- pyrroline, pyrazolidine, and imidazolidine. Additional non-limiting examples of “heterocycle” include tetrahydrofuran, 1,3-dioxolane, tetrahydrothiophene, 1,2-oxathiolane, and 1,3-oxathiolane. Additional non-limiting examples of “heterocycle” include piperidine, piperazine, tetrahydropyran, 1,4-dioxane, thiane, 1,3-dithiane, 1,4-dithiane, morpholine, and thiomorpholine. Additional non-limiting examples of “heterocycle” include indoline, tetrahydroquinoline, tetrahydroisoquinoline, and dihydrobenzofuran wherein the point of attachment for each group is on the heterocyclic ring. Wherein a substituent is a bicycle or tricycle, the bicyclic or tricyclic substituent is named using the ring by which it is attached. A heterocycle which is a bicyclic heterocycle is attached through the heterocycle: For example, e” group. However, l” group. Non-limit ycle” also include: . Additional non-limiting examples of “heterocycle” include: . . . amples of “heterocycle” also include: . include: . heterocycle” include: . Embodiments of “Aryl” In certain embodiments “aryl” is a 6-carbon aromatic group (phenyl). In certain embodiments “aryl” is a 10-carbon aromatic group (naphthyl). In certain embodiments “aryl” is a 6-carbon aromatic group fused to a heterocycle wherein the point of attachment is the aryl ring. Non-limiting examples of “aryl” include indoline, tetrahydroquinoline, tetrahydroisoquinoline, and dihydrobenzofuran wherein the point of attachment for each group is on the aromatic ring. For example is an “aryl” group. roup. Embod y y Non-limiting examples of “arylalkyl” include: an aryl group. Non-limiting examples of “arylalkyl” include: . II. ApoB BINDING LIGAND In certain embodiments, ApoB Binding Ligand is a means to bind apoB. In certain embodiments, ApoB Binding Ligand of the degrader is of Formula: -2) -4) 5) d from aryl, heteroaryl, heterocycle, and cycloalkyl; R101, R101a, R101b, R101c, and R101dare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1- C6haloalkyl, -O-C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl; R102, R102a, R102b, R102c, and R102dare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1- C6haloalkyl, -O-C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl; R103aand R103bare each independently selected from hydrogen, alkyl, haloalkyl, C0- C6alkyl-NR6R7, C0-C6alkyl-OR6, C0-C6alkyl-C(O)R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-O- C(O)R3; R104and R105are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R104aand R104bare each independently selected from hydrogen and C1-4alkyl; R106is independently selected at each instance from hydrogen, halogen, and C1-C6alkyl; or together with the carbon they are attached to, two R106groups form a C3-C6cycloalkyl; R107is independently selected at each instance from hydrogen, halogen, alkyl, haloalkyl, C0-C6alkyl-NR6R7, C0-C6alkyl-OR6, C0-C6alkyl-C(O)R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl- O-C(O)R3; or together with the carbon they are attached to, two R107groups form a C3-C6cycloalkyl; Z is C(O), S(O), S(O)2, or C(R107)2. QBis selected from bond, O, NR7, and C(R106)2; v is 1, 2, 3, or 4; w is 1, 2, 3, or 4; and R100is the attachment point to LinkerB, LinkerCor LinkerD. In certain embodiments, A is aryl. In certain embodiments, B is aryl. In certain embodiments, A is heteroaryl. In certain embodiments, B is heteroaryl. In certain embodiments, A and B are both aryl. In certain embodiments, A* is aryl. In certain embodiments, B* is aryl. In certain embodiments, A* is heteroaryl. In certain embodiments, B* is heteroaryl. In certain embodiments, A* and B* are both aryl. In certain embodiment . In certain embodiment . In certain embodiment . In certain embodiment . In certain embodiments B is . In certain embodiment . In certain embodiment In certain embodiments, R102is iodo. In certain embodiments, R101is bromo. In certain embodiments, R102is bromo. In certain embodiments, R101is trifluoromethyl. In certain embodiments, R102is trifluoromethyl. In certain embodiments, R101is methyl. In certain embodiments, R102is methyl. In certain embodiments, R101is tert-butyl. In certain embodiments, R102is tert-butyl. In certain embodiments, R101is chloro. In certain embodiments, R102is chloro. In certain embodiments, R101is trimethylsilyl. In certain embodiments, R102is trimethylsilyl. In certain embodiments, QBis CH2. In certain embodiments, QBis CF2. In certain embodiments, QBis O. In certain embodiments, R101a, R101b, R102a, and R102bare independently selected at each instance from hydrogen and iodine. In certain embodiments, R107aand R107bare each independently selected from hydrogen, halogen, alkyl, haloalkyl, and C0-C6alkyl-OR6. In certain embodiments, ApoB Binding Ligand of the degrader is selected from: . , . In certain embodiments, ApoB Binding Ligand of the degrader is selected from ,

[0007] nd In certain embodiments, ApoB Binding Ligand of the degrader is selected from , In certain embodiments, ApoB Binding Ligand of the degrader is selected from , , In certain embodiments, ApoB Binding Ligand of the degrader is selected from , In certain embodiments, ApoB Binding Ligand of the degrader is selected from nd , m , nd m nd , m , nd In certain embodiments, ApoB Binding Ligand of the degrader is selected from , . In certain embodiments, ApoB Binding Ligand of the degrader is selected from , , . In other embodiments, ApoB Binding Ligand of the degrader is selected from , , . cted from , , . cted from , , . In certain embodiments, ApoB Binding Ligand of the degrader is selected from , . In certain embodiments, the apoB degrading compound is selected from

[0008] R101a, R101b, R102a, and R102bare independently selected at each instance from hydrogen and iodine; R104aand R104bare each independently selected from hydrogen and C1-4alkyl; R107aand R107bare each independently selected from hydrogen, halogen, alkyl, haloalkyl, and C0-C6alkyl-OR6; and all other variables are as defined herein. In certain embodiments, the apoB degrading compound is selected from

[0009] lly In other embodiments, the apoB degrading compound is selected from

[0010] lly In certain embodiments, the apoB degrading compound is selected from ; In other embodiments, the apoB degrading compound is selected from ; or a ph In certain embodiments, the apoB degrading compound is selected from

[0011] In certain embodiments, the apoB degrading compound is selected from

[0012] ; or a pharmaceutically acceptable salt thereof. In other embodiments, the apoB degrading compound is selected from nd a . In certain embodiments, the apoB degrading compound is selected from r a In certain embodiments, the apoB degrading compound is selected from

[0013] nd In certain embodiments, the apoB degrading compound is selected from

[0014] nd In certain embodiments, the apoB degrading compound is selected from

[0015] ; In certain embodiments, the apoB degrading compound is selected from ; or a pharmaceutically acceptable salt thereof. In certain embodiments, ApoB Binding Ligand of the degrader is selected from 4), lected from , ; RAB1and RAB2are independently selected from hydrogen, fluorine, alkyl, and haloalkyl; RAB3is hydrogen, -OH, alkyl, -NR6R7, or =O; RAB4, RAB5, and RAB6are independently selected from hydrogen, fluorine, chlorine, bromine, alkyl, haloalkyl; and R100is the attachment point to LinkerB, LinkerCor LinkerD. In certain embodiments, RAB4is hydrogen. In certain embodiments, RAB5is hydrogen. In certain embodiments, RAB6is hydrogen. In certain embodiments, the ApoB Binding Ligand of the degrader is selected from In other embodiments, the ApoB Binding Ligand of the degrader is . In certain embodiments, the apoB degrading compound is selected from or a pharmaceutically acceptable salt thereof. In certain embodiments, the apoB degrading compound is selected from a In other embodiments, the apoB degrading compound is selected from r a p a aceu ca y accepa e sa eeo. In certain embodiments, the apoB degrading compound is selected from In certain embodiments, ApoB Binding Ligand is of Formula C-1 or C-2: -2) Z1and Z2are independently selected from CH and N; R109is selected from -C1-4alkyl-, -C2-6alkenyl-, -C0-6alkyl-S(O)2-, -C1-4acyl-, -C0-6alkyl-heteroaryl-, -C0-6alkyl-cycloalkyl, -C0-6alkyl-CO2-, -C0-6alkyl-C(O)NH-, and -C0-6alkyl-C1-4haloalkyl-; R110is hydrogen, C1-6alkyl, or C1-3haloalkyl; R111is hydrogen, C1-3alkyl, fluoro, chloro, bromo, or C1-4haloalkyl; In certain embodiments, ApoB Binding Ligand of the degrader is of Formula D-1: 1) R112is selected from C1-10alkyl, -CH2-O-, -C(O)O-, C3-8cycloalkyl, aryl, heteroaryl, bicycle, and heterocycle; R113is selected from hydrogen or -NR115R116; R114is -O-C1-6alkyl; R115and R115Bare independently C1-6alkyl; R116is C1-6alkyl; In certain embodiments, ApoB Binding Ligand of the degrader is of Formula E-1, E-2, E- 3, or E-4: 2) ) R117,R117A, and R117Bare independently selected at each instance from hydrogen, halo, -C1-6alkyl, -C1-6haloalkyl, -C1-6alkoxy, -C1-6haloalkoxy, -C2-6alkenyl, -C2-6alkynyl, -C3-8cycloalkyl, -C1-6alkyl-C3-8cycloalkyl, aryl, heteroaryl, -C1-6alkyl-aryl, -aryl-C1-6alkyl, -aryl-C1-6haloalkyl, -aryl-C3-6cycloalkyl, -aryl-C2-6alkenyl, -aryl-C2-6alkynyl, -O-aryl, -O-aryl-C1-6alkyl, -aryl-C1-6alkoxy, -arylazo, -O-heteroaryl, -heteroaryl-C1-6alkyl, -heteroaryl-C1-6haloalkyl, -heteroaryl-C1-6alkenyl, -hydroxy, -nitro, -cyano, -NH2, -NR107R108, -thiol, -C1-6alkylthio, -S-aryl, -S-heteroaryl, -C1-6alkyl-S-aryl, -C(O)-C1-6alkyl, -C(O)-aryl, -C(O)NHaryl, -C(O)O-C1-6alkyl, -C(O)NH2, -C(O)NH-C2-6alkynyl, -C(O)NH-C1-6alkyl, -C(O)-NH-C2-6alkenyl, -C(O)O-aryl, -S(O)aryl, -aryl-S(O)-C1-6alkyl, -S(O)2aryl, -S(O)2-C1-6alkyl, -aryl-S(O)2NH2, or -heteroaryl- C(O)NH2. R118is selected from is independently selected at each instance from aryl and heteroaryl; Z3and Z4are independently selected from bond, -O-, -S-, -S(O)-, -S(O)2-, -NHC(O)-, - N(C1-6alkyl)C(O)-, and -C(O)-; Z5is -O-, -S-, and NR107; R119is C1-12alkyl; R120is hydrogen, C1-6alkyl, C2-6alkenyl, aryl, C1-6haloalkyl, heteroaryl, -alkyl-heteroaryl, alkyl-aryl, alkenyl-aryl, cycloalkyl, -O-aryl, -O-alkyl, alkyl-O-aryl or alkyl-O-cycloalkyl; R121, R122, R123, R124, and R125are independently hydrogen, C1-6alkyl, halo, C1-6haloalkyl, aryl, C3-8cycloalkyl, cycloheteroalkyl, C2-6alkenyl, C2-6alkynyl, hydroxy, C1-6alkoxy, nitro, amino, thio, C1-6alkylsulfonyl, arylsulfonyl, C1-6alkylthio, arylthio, -NHC(O)-, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl, or aryloxy. In certain embodiments . In certain embodiments, the ApoB Binding Ligand of the degrader is a peptide, antibody, or antibody fragment that binds to apoB. In certain embodiments, the ApoB Binding Ligand of the degrader is an aptamer that binds apoB. SEQ ID NO: 1 GDNDSEDNSDEENC (“LP3”; Benitez-Amaro, A. et al. “Development of Innovative Antiatherosclerotic Peptides through the Combination of Molecular Modeling and a Dual (Biochemical-Cellular) Screening System” Adv. Therap.2020, 3, 2000037) SEQ ID NO: 2 GDC*DSEDNSDEC*N (C* indicating cyclic disulfide link) (Benitez- Amaro, A. et al.2000) SEQ ID NO: 3 GDC*SEDNSC*EEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 4 GC*NDSEDNSDEEC* (Benitez-Amaro, A. et al.2000) SEQ ID NO: 5 C*DNDC*EDNSDEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 6 C*DNDSEDNSDC*EN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 7 GC*NDSEDNSDC*EN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 8 GDNC*SEDNSDEEC* (Benitez-Amaro, A. et al.2000) SEQ ID NO: 9 GDNDSADNSDEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 10 GDNDSEANSDEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 11 GDNDSEDASDEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 12 GDNDSEDNSDAEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 13 GDNDSEDNSDEAN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 14 AcN-GDNDS (N-terminal acetyl group) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 15 AcN-DSEDNS (Benitez-Amaro, A. et al.2000) SEQ ID NO: 16 AcN-NSDEENC (Benitez-Amaro, A. et al.2000) SEQ ID NO: 17 ENCESC (Benitez-Amaro, A. et al.2000) SEQ ID NO: 18 AcN-SEDNSDEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 19 GDNDSEDNS (Benitez-Amaro, A. et al.2000) SEQ ID NO: 20 DSEDNSDEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 21 GDNDSEDNSDEENC (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 22 AcN-SEDNSDEEN (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 23 AcN-DSEDNSDEEN (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 24 AcN-NDSEDNDSEEN (all D-amino acids) (Benitez-Amaro, A. et al. 2000) SEQ ID NO: 25 AcN-DNDSEDNSDEEN (all D-amino acids) (Benitez-Amaro, A. et al. 2000) SEQ ID NO: 26 AcN-C*EDNSC*EE (Benitez-Amaro, A. et al.2000) SEQ ID NO: 27 AcN-SEDNADEEA (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 28 AcN-SEDNQDEEQ (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 29 AcN-SEDQDEEQ (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 30 AcN-DNDSEDNSDEEA (all D-amino acids) (Benitez-Amaro, A. et al. 2000) SEQ ID NO: 31 AcN-NDSEDNSDEEA (all D-amino acids) (Benitez-Amaro, A. et al. 2000) SEQ ID NO: 32 AcN-DSEDNSDEEA (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 33 AcN-DSEDNADEEA (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 34 AcN-DSADNADEEA (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 35 AcN-SEDNSDEENC (Benitez-Amaro, A. et al.2000) SEQ ID NO: 36 AcN-SEDNSDEENS (Benitez-Amaro, A. et al.2000) SEQ ID NO: 37 AcN-SANSDEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 38 AcN-SEANSDEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 39 AcN-SENSAEEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 40 AcN-SEDNSAEN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 41 AcN-SEDNSDAN (Benitez-Amaro, A. et al.2000) SEQ ID NO: 42 AcN-SEDRDDER (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO; 43 AcN-SEDNRDEEL (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 44 AcN-SEDNRDEEW (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 45 AcN-SEDNKDEE (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 46 AcN-DSDNKDEE (all D-amino acids) (Benitez-Amaro, A. et al.2000) SEQ ID NO: 47 AcN-DSDNKDEEA (all D-amino acids) (Benitez-Amaro, A. et al.2000) In certain embodiments, the ApoB Binding Ligand of the degrader is LP3 (SEQ ID NO: 1). In certain embodiments, the ApoB Binding Ligand of the degrader is selected from the group consisting of SEQ ID NO: 22, 23, 24, 25, 27, 28, 29, 30, 32, and 42. In certain embodiments, the ApoB Binding Ligand of the degrader is an antibody fragment comprising one, two, or three heavy chain complimentarity determining regions selected from SEQ ID NO: 48, 49, and 50, and one, two, or three light chain complimentarity determining regions selected from SEQ ID NO: 51, 52, and 53. SEQ ID NO: 48 FSNAWMSWVRQAPG (HCDR1; US20190284268A1) SEQ ID NO: 49 SSISVGGHRTYYADSVKGR (HCDR2; US20190284268A1) SEQ ID NO: 50 ARIRVGPSGGAFDY (HCDR3; US20190284268A1) SEQ ID NO: 51 CSGSNTNIGKNYVS (LCDR1; US20190284268A1) SEQ ID NO: 52 ANSNRPS (LCDR2; US20190284268A1) SEQ ID NO: 53 CASWDASLNGWV (LCDR3; US20190284268A1) In certain embodiments, the ApoB Binding Ligand of the degrader is an antibody comprising the heavy chain sequence of SEQ ID NO: 54 and the light chain sequence of SEQ ID NO: 55. SEQ ID NO: 54 EVQLLESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVSSISVGGHRT YYADSVKGRSTISRDNSKNTLYLQMNSLRAEDTAVYYCARIRVGPSGGAFDYWGQGTL VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (Heavy Chain; US20190284268A1) SEQ ID NO: 55 QSVLTQPPSASGTPGQRVTISCSGSNTNIGKNYVSWYQQLPGTAPKLLIYANSNRPSGVP DRFSGSKSGTSASLAISGLRSEDEADYYCASWDASLNGWVFGGGTKLTVLGQPKAAPS VTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYA ASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS (Light Chain; US20190284268A1) In certain embodiments, the ApoB Binding Ligand of the degrader is an antibody fragment comprising the variable heavy region (VH) amino acid sequence of SEQ ID NO: 56. In certain embodiments, the ApoB Binding Ligand of the degrader is an antibody fragment comprising the variable light region (VL) amino acid sequence of SEQ ID NO: 57. SEQ ID NO: 56 EVQLLESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVSSISVGGHRT YYADSVKGRSTISRDNSKNTLYLQMNSLRAEDTAVYYCARIRVGPSGGAFDYWGQGTL VTVS (Variable Heavy Region; US20190284268A1) SEQ ID NO: 57 QSVLTQPPSASGTPGQRVTISCSGSNTNIGKNYVSWYQQLPGTAPKLLIYANSNRPSGVP DRFSGSKSGTSASLAISGLRSEDEADYYCASWDASLNGWVFGGGTKLTVL (Variable Light Region; US20190284268A1) In certain embodiments, the ApoB Binding Ligand of the degrader is an aptamer selected from SEQ ID NO: 58-73, or an aptamer that has 90%, 95%, 97%, 98% or 99% homology with SEQ ID NO: 58-73. SEQ ID NO: 58 ATACCAGCTTATTCAATTCCGTGAGGTG GCGTATCAAC GGATATTAGG GAGAGGGGGGAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 59 ATACCAGCTTATTCAATTGTGACTGGCC ATCGATTTTA ACCCTTTTTC CTTGTGCCACAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 60 ATACCAGCTTATTCAATTGCGGTAGCAG GGCGCATTCG GATGAACATC GCCGGTGACGAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 61 ATACCAGCTTATTCAATTCCTATTCCTTATTATATTTTCTTTTTTTGTAATTTGGTCGA GATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 62 ATACCAGCTTATTCAATTCACGCTATCG GCCTTGAGAG GGTCTAAGCA ACGTATCCCAAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 63 ATACCAGCTTATTCAATTTGGGCTGGCC GAGAGTTGAC GATTTGTGCA GTCGTTAGGCAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 64 ATACCAGCTTATTCAATTCGTGAAAGGC GAACGACCAA CGGTGGAGTC TGGTTGGTGGAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 65 ATACCAGCTTATTCAATTCGCCGAAAGACAGTTAGTGTTCACTCTCGTGATGGATGG CAAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 66 ATACCAGCTTATTCAATTGGCGAGGGAG TATGTACGAC TACGTTGTAG GGTTGCTCTAAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 67 ATACCAGCTTATTCAATTGGGCGCCTGC GCTATTTGTG ATTGAAGTAA TTGAAGTGCGAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 68 ATACCAGCTTATTCAATTTGTCGTACGT GTACAGGGTA CAAAATCTCCA ATCTTGGTTAAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 69 ATACCAGCTTATTCAATTCGGAAGGGGC ATGTAAGGAC CCTGTCTGAG TGAGAACATGAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 70 ATACCAGCTTATTCAATTCGGGCGAGGA GATTGAAATC GGTAGGACCT CCTGGCCTGC GAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 71 ATACCAGCTTATTCAATTCTAAAAAGTT TCGCTCTCTC GCTCTTTATG TATGGTTTCAAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 72 ATACCAGCTTATTCAATTCCTATTCCTT ATTATATTTT CTTTTTTTGT AATTTGGTCGAGATAGTAAGTGCAATCT (WO 2023 / 177242) SEQ ID NO: 73 ATACCAGCTTATTCAATTCTATTCCTTA TTATATTTTC TTTTTTTGTA ATTTGGTCGAGATAGTAAGTGCAATCT (WO 2023 / 177242) III. PHARMACEUTICAL COMPOSITIONS AND DOSAGE FORMS FOR THE APOLIPOPROTEIN B DEGRADING COMPOUND OF THE PRESENT INVENTION An apoB degrading compound of the present invention or a pharmaceutically acceptable salt, solvate or prodrug thereof as disclosed herein can be administered as a neat chemical, but is more typically administered as a pharmaceutical composition that includes an effective amount for a host, typically a human, in need of such treatment to treat high cholesterol. In certain embodiments, the present invention provides pharmaceutical compositions comprising an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog such as a deuterated derivative, or prodrug thereof, and a pharmaceutically acceptable excipient. In certain embodiments, the apoB degrading compound is present in an effective amount, e.g., a therapeutically effective amount or a prophylactically effective amount. The ASGPR-binding apoB degrading compound of the present invention can be administered in any manner that allows the degradation of apoB. As such, examples of methods to deliver the compound of the present invention include, but are not limited to, oral, intravenous, sublingual, subcutaneous, parenteral, buccal, rectal, intra-aortal, intracranial, subdermal or transnasal, or by other means, in dosage unit formulations containing one or more conventional pharmaceutically acceptable carriers, as appropriate. In certain embodiments the apoB degrading compound of the present invention is administered orally. Typically, for oral administration the apoB degrading compound will be formulated in a solid dosage form for oral administration or as a gel containing capsule. Non- limiting examples of solid dosage forms include capsules, tablets, and powders. In certain embodiments the apoB degrading compound of the present invention is administered intravenously. For example, the apoB degrading compound may be formulated in a liquid dosage form for intravenous injection, such as a buffered solution. Non-limiting examples of solutions for intravenous injection include phosphate buffered solution and saline buffered solution. In certain embodiments the solution is buffered with multiple salts. In certain embodiments the apoB degrading compound of the present invention is administered subcutaneously. Typically, the apoB degrading compound will be formulated in a liquid dosage form for subcutaneous injection, such as a buffered solution. Non-limiting examples of solutions for subcutaneous injection include phosphate buffered solution and saline buffered solution. In certain embodiments the solution is buffered with multiple salts. Therefore, the disclosure provides pharmaceutical compositions comprising an effective amount of an apoB degrading compound or its pharmaceutically acceptable salt together with at least one pharmaceutically acceptable carrier for any appropriate use thereof. The pharmaceutical composition may contain an apoB degrading compound or salt as the only active agent, or, in an alternative embodiment, the apoB degrading compound and at least one additional active agent. In certain embodiments the term pharmaceutically acceptable salt refers to a salt of the described apoB degrading compound which is, within the scope of sound medical judgment, suitable for administration to a host such as a human without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit / risk ratio, and effective for its intended use. These salts can be prepared during the final isolation and purification of the apoB degrading compound or by separately reacting the apoB degrading compound in its free form with a suitable organic or inorganic acid and then isolating the salt thus formed. Basic compounds are capable of forming a wide variety of different salts with various inorganic and organic acids. Acid addition salts of the basic apoB degrading compounds are prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt in the conventional manner. The free base form can be regenerated by contacting the salt form with a base and isolating the free base in the conventional manner. The free base forms may differ from their respective salt forms in certain physical properties such as solubility in polar solvents. Pharmaceutically acceptable base addition salts may be formed with metals or amines, such as alkali and alkaline earth metal hydroxides, or of organic amines. Examples of metals used as cations, include, but are not limited to, sodium, potassium, magnesium, calcium, and the like. Examples of suitable amines include, but are not limited to, N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, N-methylglucamine, and procaine. The base addition salts of acidic apoB degrading compounds are prepared by contacting the free acid form with a sufficient amount of the desired base to produce the salt in the conventional manner. The free acid form can be regenerated by contacting the salt form with an acid and isolating the free acid in a conventional manner. The free acid forms may differ from their respective salt forms somewhat in certain physical properties such as solubility in polar solvents. Salts can be prepared from inorganic acids sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, nitric, phosphoric, sulfuric, hydrobromic, hydriodic, phosphorus, and the like. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate mesylate, glucoheptonate, lactobionate, laurylsulphonate and isethionate salts, and the like. Salts can also be prepared from organic acids, such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, etc. and the like. Representative salts include acetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, maleate, tartrate, methanesulfonate, and the like. Pharmaceutically acceptable salts can include cations based on the alkali and alkaline earth metals, such as sodium, lithium, potassium, calcium, magnesium and the like, as well as non-toxic ammonium, quaternary ammonium, and amine cations including, but not limited to, ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. Also contemplated are the salts of amino acids such as arginate, gluconate, galacturonate, and the like. See, for example, Berge et al., J. Pharm. Sci., 1977, 66, 1-19. Pharmaceutically acceptable excipients include inert diluents, dispersing and / or granulating agents, surface active agents and / or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and / or oils. Additional acceptable excipients include cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, perfuming agents, etc., and combinations thereof. Exemplary diluents include calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, etc., and combinations thereof. Exemplary granulating and / or dispersing agents include potato starch, corn starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose and wood products, natural sponge, cation–exchange resins, calcium carbonate, silicates, sodium carbonate, cross–linked poly(vinyl–pyrrolidone) (crospovidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethyl cellulose, cross–linked sodium carboxymethyl cellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (Veegum), sodium lauryl sulfate, quaternary ammonium compounds, etc., and combinations thereof. Exemplary surface active agents and / or emulsifiers include natural emulsifiers (e.g. acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g. bentonite [aluminum silicate] and Veegum [magnesium aluminum silicate]), long chain amino acid derivatives, high molecular weight alcohols (e.g. stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g. carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxyvinyl polymer), carrageenan, cellulosic derivatives (e.g. carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g. polyoxyethylene sorbitan monolaurate [Tween 20], polyoxyethylene sorbitan [Tween 60], polyoxyethylene sorbitan monooleate [Tween 80], sorbitan monopalmitate [Span 40], sorbitan monostearate [Span 60], sorbitan tristearate [Span 65], glyceryl monooleate, sorbitan monooleate [Span 80]), polyoxyethylene esters (e.g. polyoxyethylene monostearate [Myrj 45], polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and Solutol), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g., Cremophor), polyoxyethylene ethers, (e.g. polyoxyethylene lauryl ether [Brij 30]), poly(vinyl–pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, Pluronic F 68, Poloxamer 188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, etc. and / or combinations thereof. Exemplary binding agents include starch (e.g. cornstarch and starch paste), gelatin, sugars (e.g. sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol, etc.), natural and synthetic gums (e.g. acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl–pyrrolidone), magnesium aluminum 32 silicate (Veegum), and larch arabogalactan), alginates, polyethylene oxide, polyethylene glycol, inorganic calcium salts, silicic acid, polymethacrylates, waxes, water, alcohol, etc., and / or combinations thereof. Exemplary preservatives include antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, alcohol preservatives, acidic preservatives, etc., and / or combinations thereof. Exemplary antioxidants include alpha tocopherol, ascorbic acid, acorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, and sodium sulfite. Any dosage form can be used that achieves the desired results. In certain embodiments the pharmaceutical composition is in a dosage form that contains from about 0.1 mg to about 1000 mg, from about 5 mg to about 750 mg, from about 10 mg to about 750 mg, from about 1 mg to about 500 mg, from about 5 mg to about 500 mg, from about 10 mg to about 500 mg, from about 1 mg to about 250 mg, from about 5 mg to about 250 mg, from about 10 mg to about 250 mg, from about 25 mg to about 800 mg, from about 50 mg to about 800 mg, from about 75 mg to about 800 mg, from about 100 mg to about 800 mg, or from about 100 mg to about 600 mg of the apoB degrading compound. In other embodiments, optionally from about 0.1 mg to about 1000 mg, from about 1 mg to about 750 mg, from about 5 mg to about 750 mg, from about 10 mg to about 750 mg, from about 1 mg to about 500 mg, from about 5 mg to about 500 mg, from about 10 mg to about 500 mg, from about 1 mg to about 250 mg, from about 5 mg to about 250 mg, from about 10 mg to about 250 mg, from about 25 mg to about 800 mg, from about 50 mg to about 800 mg, from about 75 mg to about 800 mg, from about 100 mg to about 800 mg, or from about 100 mg to about 600 mg of an additional active agent in a unit dosage form. Examples are dosage forms with at least about 0.1, 1, 5, 10, 25, 50, 100, 200, 250, 300, 400, 500, 600, 700, 750, 800, 850, 900, 950, or 1,000 mg of the apoB degrading compound, or its salt. In certain embodiments the dosage form has at most about 0.1, 1, 5, 10, 25, 50, 100, 200, 250, 300, 400, 500, 600, 700, 750, 800, 850, 900, 950, or 1,000 mg of the apoB degrading compound, or its salt. In certain embodiments the dose ranges from about 0.01-100 mg / kg of patient bodyweight, for example at least about 0.01 mg / kg, about 0.05 mg / kg, about 0.1 mg / kg, about 0.5 mg / kg, about 1 mg / kg, about 1.5 mg / kg, about 2 mg / kg, about 2.5 mg / kg, about 3 mg / kg, about 3.5 mg / kg, about 4 mg / kg, about 4.5 mg / kg, about 5 mg / kg, about 10 mg / kg, about 15 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, about 55 mg / kg, about 60 mg / kg, about 65 mg / kg, about 70 mg / kg, about 75 mg / kg, about 80 mg / kg, about 85 mg / kg, about 90 mg / kg, about 95 mg / kg, or about 100 mg / kg. In some embodiments, the apoB degrading compound disclosed herein or used as described are administered once per week, twice per week, or three or more times per week. In some embodiments, the apoB degrading compound disclosed herein or used as described are administered once a day (QD), twice a day (BID), or three times a day (TID). In some embodiments, the apoB degrading compound disclosed herein or used as described are administered at least once a day for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days, at least 17 days, at least 18 days, at least 19 days, at least 20 days, at least 21 days, at least 22 days, at least 23 days, at least 24 days, at least 25 days, at least 26 days, at least 27 days, at least 28 days, at least 29 days, at least 30 days, at least 31 days, at least 35 days, at least 45 days, at least 60 days, at least 75 days, at least 90 days, at least 120 days, at least 150 days, at least 180 days, or longer. In certain embodiments, the apoB degrading compound of the present invention is administered at least once a day, twice a day, three times a day, or four times a day. In certain embodiments, the apoB degrading compound of the present invention is administered up to once, twice, or three times per week. In certain embodiments, the apoB degrading compound of the present invention is administered at least once, twice, three times, or four times per week. The pharmaceutical composition may be formulated as any pharmaceutically useful form, e.g., a pill, capsule, tablet, an injection or infusion solution, a syrup, an inhalation formulation, a suppository, a buccal or sublingual formulation, a parenteral formulation, or in a medical device. Some dosage forms, such as tablets and capsules, can be subdivided into suitably sized unit doses containing appropriate quantities of the active components, e.g., an effective amount to achieve the desired purpose. Carriers include excipients and diluents and must be of sufficiently high purity and sufficiently low toxicity to render them suitable for administration to the patient being treated. The carrier can be inert, or it can possess pharmaceutical benefits of its own. The amount of carrier employed in conjunction with the apoB degrading compound is sufficient to provide a practical quantity of material for administration per unit dose of the apoB degrading compound. If provided as in a liquid, it can be a solution or a suspension. Representative carriers include phosphate buffered saline, water, solvent(s), diluents, pH modifying agents, preservatives, antioxidants, suspending agents, wetting agent, viscosity agents, tonicity agents, stabilizing agents, and combinations thereof. In some embodiments, the carrier is an aqueous carrier. Examples of aqueous carries include, but are not limited to, an aqueous solution or suspension, such as saline, plasma, bone marrow aspirate, buffers, such as Hank’s Buffered Salt Solution (HBSS), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), Ringers buffer, ProVisc®, diluted ProVisc®, Provisc® diluted with PBS, Krebs buffer, Dulbecco’s PBS, normal PBS, sodium hyaluronate solution (HA, 5 mg / mL in PBS), citrate buffer, simulated body fluids, plasma platelet concentrate and tissue culture medium or an aqueous solution or suspension comprising an organic solvent. Acceptable solutions include, for example, water, Ringer’s solution and isotonic sodium chloride solutions. The formulation may also be a sterile solution, suspension, or emulsion in a non-toxic diluent or solvent such as 1,3-butanediol. Viscosity agents may be added to the pharmaceutical composition to increase the viscosity of the composition as desired. Examples of useful viscosity agents include, but are not limited to, hyaluronic acid, sodium hyaluronate, carbomers, polyacrylic acid, cellulosic derivatives, polycarbophil, polyvinylpyrrolidone, gelatin, dextin, polysaccharides, polyacrylamide, polyvinyl alcohol (including partially hydrolyzed polyvinyl acetate), polyvinyl acetate, derivatives thereof and mixtures thereof. Solutions, suspensions, or emulsions for administration may be buffered with an effective amount necessary to maintain a pH suitable for the selected administration. Suitable buffers are well known by those skilled in the art. Some examples of useful buffers are acetate, borate, carbonate, citrate, and phosphate buffers. Solutions, suspensions, or emulsions for topical, for example, ocular administration may also contain one or more tonicity agents to adjust the isotonic range of the formulation. Suitable tonicity agents are well known in the art. Some examples include glycerin, mannitol, sorbitol, sodium chloride, and other electrolytes. Classes of carriers include, but are not limited to binders, buffering agents, coloring agents, diluents, disintegrants, emulsifiers, flavorants, glidants, lubricants, preservatives, stabilizers, surfactants, tableting agents, and wetting agents. Some carriers may be listed in more than one class, for example vegetable oil may be used as a lubricant in some formulations and a diluent in others. Exemplary pharmaceutically acceptable carriers include sugars, starches, celluloses, powdered tragacanth, malt, gelatin, talc, and vegetable oils. Optional active agents may be included in a pharmaceutical composition, which do not substantially interfere with the activity of the apoB degrading compound of the present invention. The pharmaceutical compositions / combinations can be formulated for oral administration. These compositions can contain any amount of the apoB degrading compound that achieves the desired result, for example between 0.1 and 99 weight % (wt.%) of the apoB degrading compound and usually at least about 5 wt.% of the apoB degrading compound. Some embodiments contain from about 25 wt.% to about 50 wt. % or from about 5 wt.% to about 75 wt.% of the apoB degrading compound. Enteric coated oral tablets may also be used to enhance bioavailability of the apoB degrading compound for an oral route of administration. Formulations suitable for rectal administration are typically presented as unit dose suppositories. These may be prepared by admixing the apoB degrading compound with one or more conventional solid carriers, for example, cocoa butter, and then shaping the resulting mixture. ApoB degrading compounds of the present invention and pharmaceutically acceptable composition, salts, isotopic analogs, or prodrugs thereof, may be formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions comprising an apoB degrading compound as described herein will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject or organism will depend upon a variety of factors including the disease, disorder, or condition being treated and the severity of the disorder; the activity of the specific the apoB degrading compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the subject; the time of administration, route of administration, and rate of excretion of the apoB degrading compound employed; the duration of the treatment; drugs used in combination or coincidental with the apoB degrading compound employed; and like factors well known in the medical arts. The apoB degrading compound and compositions provided herein can be administered by any route, including enteral (e.g., oral), parenteral, systemic, intravenous, intramuscular, intra– arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and / or drops), mucosal, nasal, buccal, sublingual; by intratracheal instillation, bronchial instillation, and / or inhalation; and / or as an oral spray, nasal spray, and / or aerosol. Specifically contemplated routes are oral administration, intravenous administration (e.g., systemic intravenous injection), regional administration via blood and / or lymph supply, and / or direct administration to an affected site. In general, the most appropriate route of administration will depend upon a variety of factors including the nature of the agent (e.g., its stability in the environment of the gastrointestinal tract), the condition of the subject (e.g., whether the subject is able to tolerate oral administration). The exact amount of an apoB degrading compound required to achieve an effective amount will vary from subject to subject, depending, for example, on species, age, and general condition of a subject, severity of the side effects or disorder, identity of the particular apoB degrading compound(s), mode of administration, and the like. The desired dosage can be delivered using any frequency determined to be useful by the health care provider, including three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dosage can be delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations). It will be also appreciated that an apoB degrading compound or composition, as described herein, can be administered in combination with one or more additional therapeutically active agents. The apoB degrading compound or compositions can be administered in combination with additional therapeutically active agents that improve their bioavailability, reduce and / or modify their metabolism, inhibit their excretion, and / or modify their distribution within the body. It will also be appreciated that the therapy employed may achieve a desired effect for the same disorder (for example, an apoB degrading compound can be administered in combination with an anti– inflammatory agent, anti–cancer agent, immunosuppressant, etc.), and / or it may achieve different effects (e.g., control of adverse side–effects, e.g., emesis controlled by an antiemetic). The apoB degrading compound or composition can be administered concurrently with, prior to, or subsequent to, one or more additional therapeutically active agents. In general, each agent will be administered at a dose and / or on a time schedule determined for that agent. It will further be appreciated that the additional therapeutically active agent used in this combination can be administered together in a single composition or administered separately in different compositions. The particular combination to employ in a regimen will take into account compatibility of the apoB degrading compound with the additional therapeutically active agent and / or the desired therapeutic effect to be achieved. In general, it is expected that additional therapeutically active agents used in combination be used at levels that do not exceed the levels at which they are used individually. In some embodiments, the levels used in combination will be lower than those used individually. Exemplary additional therapeutically active agents include, but are not limited to, small organic molecules such as drug compounds (e.g., compounds approved by the Food and Drugs Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins and cells. In certain embodiments, the additional therapeutically active agent is an anti-cancer agent, e.g., radiation therapy and / or one or more chemotherapeutic agents. In certain aspects, a treatment regimen is provided comprising the administration of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog (such as a deuterated derivative), or prodrug thereof in combination or in alternation with at least one additional therapeutic agent. The combinations and / or alternations can be administered for beneficial, additive, or synergistic effect in the treatment of a disorder which is caused or exacerbated by high levels of apoB, LDL, VLDL, or a combination thereof in circulation. IV. ASGPR BINDING LIGANDS In certain embodiments the ASGPR Binding Ligand is selected from: . from: . from: . In certain embodiments the ASGPR Binding Ligand is selected from:

[0016] . ; R201is C0-C6alkyl-cyano, alkyl, alkenyl, alkynyl, haloalkyl, F, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, and C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from R80. In certain embodiments, the ASGPR Binding Ligand is selected from: In another aspect the ASGPR Binding Ligand for use in a compound of Formula I, Formula II, or Formula III is a compound selected from: ; wherein Q2is selected from -O-, -N(R10)-, S, S(O), C(R4a)(R4b), and S(O)2; L is selected from ; is heteroaryl or phenyl, each of which is optionally substituted with 1 or 2 substitu independently selected from R65; R3cis selected from the group consisting of hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, -OR8, and -NR8R9; R4ais selected from hydrogen, alkyl, haloalkyl, and halogen; and R4bis selected from hydrogen, alkyl, haloalkyl, halogen, C0-C6alkyl-OR6, C0-C6alkyl-SR6, and C0-C6alkyl-NR6R7. In certain embodiments the ASGPR Binding Ligand for use in a compound of Formula I, Formula II, or Formula III is a compound selected from: ,

[0017] , and ; wherei R301, R301b, and R305are independently selected from hydrogen, C0-C6alkyl-cyano, alkyl, alkenyl, alkynyl, haloalkyl, F, Cl, Br, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, and C0-C6alkylN3, each of which except hydrogen, F, Cl, and Br is optionally substituted with 1 or 2 substituents independently selected at each occurrence from R99; R301cis selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, -C(O)R3, -S(O)R3, -C(S)R3, and -S(O)2R3; wherein one of R301, R301b, R301c, and R305is replaced with a bond to LinkerA; L is selected from ; R3a, R3b, R3c, and rence from hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, -OR8, and -NR8R9; R322is selected from bond, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, and C2-C4 alkynyl; R323 is selected from bond , , C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, and C2-C4 alkynyl; R75, R76, R77, R78, and R79are independently selected at each instance from hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-OR6, C0- C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, -N=S(O)(R3)2, C0-C6alkylN3, heteroaryl, and aryl, each of which is optionally substituted with 1 or 2 substituents independently selected at each occurrence from R99b; n, m, and p are independently 0, 1, or 2; q is 1, 2, or 3; In certain embodiments, A* is aryl. In certain embodiments, B* is aryl. In certain embodiments, A* is heteroaryl. In certain embodiments, B* is heteroaryl. is aryl, heterocycle, cycloalkyl, or heteroaryl; is aryl, heterocycle, cycloalkyl, bicycle, or heteroaryl; is aryl or heteroaryl; , Y is CH, CR75, or N; Z is selected from -O-, -NR6-, -S-, -S(O)-, -S(O)2-, and -CR3aR3b-; and R99and R99bare independently selected at each instance from alkyl (including C1-C4alkyl), alkenyl (including C2-C4alkenyl), alkynyl (including C2-C4alkynyl), haloalkyl (including C1- C4haloalkyl), -OR6, F, Cl, Br, I, -NR6R7, -NR8R9, heterocycle, heteroaryl, aryl, cyano, nitro, hydroxyl, azide, amide, -SR3, -S(O)(NR6)R3, -NR8C(O)R3, -C(O)NR6R7, -C(O)OR3, -C(O)R3, and -SF5. In another aspect the ASGPR Binding Ligand for use in a compound of Formula I, Formula II, or Formula III is a compound selected from: ; R47is selected from OH, -N3, N(R48a)(R48b), N(R48a)-C(O)-R48b, N(R48a)-C(O)- N(R48b)(R48c), N(R48a)-C(O)-OR48b, N(R48a)-S(O)2-R48b, tetrazole, or triazole, wherein the tetrazole and triazole are optionally substituted with one R48asubstituent; R48a, R48b, and R48care each independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6alkenyl, C1-C6alkynyl, C2-C6haloalkenyl, and C2-C6haloalkynyl, wherein one or two - CH2- groups of the alkyl may be replaced with a heteroatom group independently selected from - O-, -S-, and -N(R52a)- and wherein one or two -CH3 groups of the alkyl may be independently replaced with a heteroatom group selected from -N(R52a)(R52a), -OR52a, and -SR52awherein the heteroatom groups are separated by at least 2 carbon atoms; and R52aand R52bare each independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkenyl, C1-C6 alkynyl, C2-C6 haloalkenyl, and C2-C6 haloalkynyl. In alternative embodiments, R1and R5are independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, halogen, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-cyano, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl- NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0- C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)- S(O)2R3, C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, or C0-C6alkyl-O-S(O)2R3, each of which except hydrogen is optionally substituted as allowed by valence with 1, 2, or 3 substituents independently selected from R80. In alternative embodiments, R6and R7are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3, each of which except hydrogen is optionally substituted as allowed by valence with 1, 2, or 3 substituents independently selected from R80; In alternative embodiments, R8and R9are independently selected at each occurrence from hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocycle, each of which except hydrogen is optionally substituted as allowed by valence with 1, 2, or 3 substituents independently selected from R80; Embodiments of R301In certain embodiments R301is a bond to LinkerA. In certain embodiments R301is hydrogen. In certain embodiments R301is . In certain embodiments R301is . In certain embodiments R301is . In certain embodiments R301is . In certain embodiments R301is . In certain embodiments R301is . In certain embodiments R is C0-C6alkyl-cyano. In certain embodiments R301is alkyl. In certain embodiments R301is alkenyl. In certain embodiments R301is alkynyl. In certain embodiments R301is haloalkyl. In certain embodiments R301is F. In certain embodiments R301is Cl. In certain embodiments R301is Br. In certain embodiments R301is aryl. In certain embodiments R301is arylalkyl. In certain embodiments R301is heteroaryl. In certain embodiments R301is heteroarylalkyl. In certain embodiments R301is heterocycle. In certain embodiments R301is heterocycloalkyl. In certain embodiments R301is haloalkoxy. Embodiments of R301bIn certain embodiments R301bis a bond to LinkerA. In certain embodiments R301bis hydrogen. In certain embodiments R301bis . In certain embodiments R301bis . In certain embodiments R301bis . In certain embodiments R301bis . In certain embodiments R301bis . In certain embodiments R301bis . In certain embodiments R is C0-C6alkyl-cyano. In certain embodiments R301bis alkyl. In certain embodiments R301bis alkenyl. In certain embodiments R301bis alkynyl. In certain embodiments R301bis haloalkyl. In certain embodiments R301bis F. In certain embodiments R301bis Cl. In certain embodiments R301bis Br. In certain embodiments R301bis aryl. In certain embodiments R301bis arylalkyl. In certain embodiments R301bis heteroaryl. In certain embodiments R301bis heteroarylalkyl. In certain embodiments R301bis heterocycle. In certain embodiments R301bis heterocycloalkyl. In certain embodiments R301bis haloalkoxy. Embodiments of R305In certain embodiments R305is a bond to LinkerA. In certain embodiments R305is hydrogen. In certain embodiments R305is . In certain embodiments R305is . In certain embodiments R305is . In certain embodiments R305is . In certain embodiments R305is . In certain embodiments R305is . In certain embodiments R is C0-C6alkyl-cyano. In certain embodiments R305is alkyl. In certain embodiments R305is alkenyl. In certain embodiments R305is alkynyl. In certain embodiments R305is haloalkyl. In certain embodiments R305is F. In certain embodiments R305is Cl. In certain embodiments R305is Br. In certain embodiments R305is aryl. In certain embodiments R305is arylalkyl. In certain embodiments R305is heteroaryl. In certain embodiments R305is heteroarylalkyl. In certain embodiments R305is heterocycle. In certain embodiments R305is heterocycloalkyl. In certain embodiments R305is haloalkoxy. In another aspect the ASGPR Binding Ligand for use in a compound of Formula I, Formula II, or Formula III is a compound selected from: ; R47is selected from OH, -N3, N(R48a)(R48b), N(R48a)-C(O)-R48b, N(R48a)-C(O)- N(R48b)(R48c), N(R48a)-C(O)-OR48b, N(R48a)-S(O)2-R48b, tetrazole, or triazole, wherein the tetrazole and triazole are optionally substituted with one R48asubstituent; R48a, R48b, and R48care each independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6alkenyl, C1-C6alkynyl, C2-C6haloalkenyl, and C2-C6haloalkynyl, wherein one or two - CH2- groups of the alkyl may be replaced with a heteroatom group independently selected from - O-, -S-, and -N(R52a)- and wherein one or two -CH3 groups of the alkyl may be independently replaced with a heteroatom group selected from -N(R52a)(R52a), -OR52a, and -SR52awherein the heteroatom groups are separated by at least 2 carbon atoms; R52aand R52bare each independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkenyl, C1-C6 alkynyl, C2-C6 haloalkenyl, and C2-C6 haloalkynyl, In certain embodiments the ASGPR Binding Ligand is selected from: . . In certain embodiments the ASGPR Binding Ligand is selected from: . . . . . In certain embodiments the ASGPR Binding Ligand is selected from: . described in: Reshitko, G. S., et al., “Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor,” Bioconjugate Chem. 2020, 31, 5, 1313–1319; Majouga, A. G., et al., “Identification of Novel Small- Molecule ASGP-R Ligands,” Current Drug Delivery, 2016, 13, 1303-1312; Olshanova, A. S., et al., “Synthesis of a new betulinic acid glycoconjugate with N-acetyl-D-galactosamine for the targeted delivery to hepatocellular carcinoma cells,” Russian Chemical Bulletin, International Edition, Vol.69, No.1, pp.158 — 163, January 2020; Yamansarov, E. Yu., et al., “New ASGPR-targeted ligands based on glycoconjugated natural triterpenoids,” Russian Chemical Bulletin, International Edition, Vol.68, No. 12, pp. 2331 — 2338, December 2019; Congdon, M. D., et al., “Enhanced Binding and Reduced Immunogenicity of Glycoconjugates Prepared via Solid-State Photoactivation of Aliphatic Diazirine Carbohydrates,” Bioconjugate Chem.2021, 32, 1, 133–142; and Dhawan, V., et al., “Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting - Synthesis and comparative in silico and in vitro assessment,” Carbohydrate Research 509 (2021) 108417. In some embodiments, the ASGPR Binding Ligand can be a moiety having the structure of M1, M2, M3, or M4, or a combination thereof. In various embodiments, ASGPR Binding Ligand M1 to M4 can be conjugated to any suitable Linker as described herein and in Congdon, M. D., et al., “Enhanced Binding and Reduced Immunogenicity of Glycoconjugates Prepared via Solid- State Photoactivation of Aliphatic Diazirine Carbohydrates,” Bioconjugate Chem.2021, 32, 1, 133–142. In some embodiments, the ASGPR Binding Ligand and Linker can be a moiety having the structure of M5 : 5. ndently at each occurre1 2 nce R * or R *, of Formula I, Formula II, or Formula III contain an ASGPR Binding Ligand with the structure of M5. In various embodiments, each R* in M5 is R1*. In various embodiments, each R* in M5 is R2*. In various embodiments, ASGPR Binding Ligand M5 can be conjugated / bonded to any suitable Linker as described herein and in Reshitko, G. S., et al., “Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor,” Bioconjugate Chem.2020, 31, 5, 1313–1319. In various embodiments, the ASGPR Binding Ligand can be the galactose behenic acid ester-derived moiety M7: n e s rucure , s H or NHAc. In various embodiments, the ASGPR Binding Ligand can be the agarose behenic acid ester-derived moiety M8:

[0018] d can be any of the compounds 2-18 below: In various embodiments, R is CH2OAc, COOH, or CH2OH. Non-limiting examples of methods to conjugate these ASGPR Binding Ligands are provided in Majouga, A. G., et al., “Identification of Novel Small-Molecule ASGP-R Ligands,” Current Drug Delivery, 2016, 13, 1303-1312; Olshanova, A. S., et al., “Synthesis of a new betulinic acid glycoconjugate with N- acetyl-D-galactosamine for the targeted delivery to hepatocellular carcinoma cells,” Russian Chemical Bulletin, International Edition, Vol. 69, No. 1, pp. 158 — 163, January 2020; Yamansarov, E. Yu., et al., “New ASGPR-targeted ligands based on glycoconjugated natural triterpenoids,” Russian Chemical Bulletin, International Edition, Vol. 68, No. 12, pp. 2331 — 2338, December 2019. In certain aspects these ASGPR Binding Ligands can be attached to a LinkerAthrough or by reaction with at least one OH, NH, vinyl, alkynyl, amide, acid, ester, ketone, or aromatic halogen. Suitable reaction modes include, but are not limited to, substitution (e.g. alkylation of OH or NH groups), esterification (forming an ester), amidation (forming an amide), transesterification (exchanging one ester for another), transamidation (exchanging one amide for another), azide-alkyne cycloaddition, and other reactions capable of forming C-C, N-C, or O-C bonds with vinyl and alkynyl groups such as cycloadditions, aminations, oxidations, alkylations, rearrangement reactions (e.g. Claisen, Cope, etc.), and the like. In certain embodiments the compound of the present invention is:

[0019] or or a pharm . In certain embodiments the compound of the present invention is: or a pharmaceuti In certain embodiments the compound of the present invention is: or a pharma In certain embodiments the compound of the present invention is:

[0020] or a pharmaceutica In certain aspects the invention provides a bidentate version of a monodentate embodiment presented herein. For example, in this aspect the bidentate of the following embodiment

[0021] . monodentate embodiment presented herein. For example, in this aspect the tridentate of the following embodiment . In certain aspects an apoB degrading compound delivering compound of Formula IB, Formula IIB, or Formula IIIB is provided: B) B) IIB); or a pharma y wherein ASGPR Binding LigandBis a compound selected from:

[0022] ; all other variables are defined herein. Embodiments of the Linker In non-limiting embodiments, LinkerAand LinkerBare independently selected from: ; wherein: R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are independently at each occurrence selected from the group consisting of a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO2-, -S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, -P(O)(R3)O-, -P(O)(R3)-, a divalent residue of a natural or unnatural amino acid, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, -CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O- (CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, -[C(O)-CH2-O]n-, a divalent residue of a fatty acid, a divalent residue of an unsaturated or saturated mono- or di-carboxylic acid; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, hydroxyl, alkoxy, azide, amino, cyano, -NR6R7, -NR8SO2R3, -NR8S(O)R3, haloalkyl, aryl, heteroaryl, and heterocycle; and the remaining variables are as defined herein. In one embodiment LinkerBis bond and LinkerAis . B nd Linker is . R16, R17, R18, R19, and R20provided herein the structure can be included in the Linker as read from left to right or alternatively as read from right to left unless excluded by context. For example, when R15i and LinkerBis be To save page space, certain embodiments of are described as embodiments of LinkerAbodiments of LinkerAdescribed herein are also embodiments of LinkerBand embodiments of LinkerBdescribed herein are also embodiments of LinkerA. In certain embodiments, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consisting of bond, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NR6- , -NR6C(O)-, -O-, -NR6-, -C(R21R21)-, a divalent residue of a natural or unnatural amino acid, - CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O-(CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, -[C(O)-CH2-O]n-, -[-NR6C(R21R21)C(O)O-]xx-, and a divalent residue of a fatty acid; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21. In certain embodiments, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consisting of bond, -O-, -NR6-, -C(R21R21)-, -CH2CH2- [O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O-(CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, and -[C(O)-CH2-O]n-; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21. In certain embodiments, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consisting of bond, -O-, -C(R21R21)-, -CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O-(CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, and -[C(O)-CH2-O]n-; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21. In certain embodiments, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consisting of bond, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NR6- , -NR6C(O)-, -O-, -NR6-, -C(R21R21)-, a divalent residue of a natural or unnatural amino acid, - CH2CH2-[O-(CH2)2]n-NR6-, and -[-NR6C(R21R21)C(O)O-]xx-; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21. In alternative embodiments, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consisting of bond, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NR6- , -NR6C(O)-, -O-, -NR6-, -C(R21R21)-, a divalent residue of a natural or unnatural amino acid, - CH2CH2-[O-(CH2)2]n-NR6-, and -[-NR6C(R21R21)C(O)-]xx-; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21. In certain embodiments, LinkerAis selected from In one embodiment, a divalent residue of an amino acid is selected from , and . mino acid can be oriented in either direction and wherein the amino acid can be in the L- or D-form. be In alternative embodiments, LinkerA, LinkerB, LinkerC, or LinkerDcomprises a polymer linker. In certain embodiments, the polymer linker is a copolymer. In certain embodiments the polymer linker is a block copolymer linker. In certain embodiments, the polymer linker is an alternating copolymer linker. In certain embodiments, the polymer linker is a random copolymer. In certain embodiments, the polymer linker is not branched. In certain embodiments, the polymer linker is branched. For example, a polymer comprising ethylene glycol monomers does not have a branch point. However, a polymer comprising propylene glycol monomers contains a branch point. In certain embodiments, a branch point is an R21group. In certain embodiments, the polymer linker has one branch point. In certain embodiments, the polymer linker has two, three, four, five, six, seven, eight, nine, or ten branch points. In certain embodiments, the R11, R12, R13, R14, R15, R16, R17, R18, R19, or R20group is branched by one R21group. In certain embodiments, the R11, R12, R13, R14, R15, R16, R17, R18, R19, or R20group is branched by two R21groups. In certain embodiments, the R11, R12, R13, R14, R15, R16, R17, R18, R19, or R20group is branched by three R21groups. In certain embodiments, the R11, R12, R13, R14, R15, R16, R17, R18, R19, or R20group is branched by four R21groups. For example, when R11is -[-(CH2)2-O-]n-, the ethylene glycol monomer can be mono-, di-, or tribranched depending on the number of R21substituents and regiochemistry of R21substituents: . Linker monomers of different structures can be combined in a repeating or random pattern and can be oriented in either direction such that a stable compound results. For example, if R13, R15, R17are -[-(CH2)2-O-]n- substituted by one R21group; R14, R16, and R18are -[-NR6C(R21aR21b)C(O)-]xx-; n is 3; xx is 3; R21is CH3, R21aand R21bare hydrogen; and R6is CH3; the alternating block copolymer linker would be of the formula: . 9 , and R20are independently at each occurrence selected from the group consisting of a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-,-SO2-, -S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21aR21b)-, -P(O)(R3)O-, -P(O)(R3)-, a divalent residue of a natural or unnatural amino acid, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, -CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n- NR6-, -CH2CH2-[O-(CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, -[C(O)-CH2-O]n-, -[-NR6C(R21aR21b)C(O)O-]xx- a divalent residue of a fatty acid, a divalent residue of an unsaturated or saturated mono- or di- , and , , , tly selected from R21; wherein za, zb, zc, zd, ze, zf, zg, zh, zi, and zj are independently selected at each instance from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, and wherein the sum of za, zb, zc, zd, ze, zf, zg, zh, zi, and zj is not more than 50. In certain embodiments, the sum of the sum of za, zb, zc, zd, ze, zf, zg, zh, zi, and zj is not more than 30. In certain embodiments, the sum of za, zb, zc, zd, ze, zf, zg, zh, zi, and zj is not more than 25. In certain embodiments, the sum of za, zb, zc, zd, ze, zf, zg, zh, zi, and zj is not more than 15. In certain embodiments, the sum of za, zb, zc, zd, ze, zf, zg, zh, zi, and zj is not more than 10. In alternative embodiments, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are independently at each occurrence selected from the group consisting of a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-,-SO2-, -S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21aR21b)-, -P(O)(R3)O-, -P(O)(R3)-, a divalent residue of a natural or unnatural amino acid, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, -CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O-(CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, -[C(O)-CH2-O]n-, -[-NR6C(R21aR21b)C(O)-]xx- a divalent residue of a fatty acid, a divalent residue of an unsaturated , , ntly selected from R21;

[0023] For example, a polymer linker can comprise an alternating block copolymer of the formula Linker monomers can be oriented in either direction. For example, when R15is ,za is four, B , then LinkerBcan be: nd n certa n embod ments, t e po ymer n er s a random copo ymer. random copolymer linker is a linker without a repeating pattern of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20monomer groups. In some embodiments, a random copolymer linker has different groups for each of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20. In certain embodiments, two, three, four or five of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20in a random copolymer linker are the same group, but are present in a random order. For example, a random block copolymer linker can comprise a polymer of the formula . In certain embodiments, the random copolymer linker is a polymer linker comprised of up to 50, up to 30, up to 25, up to 20, or up to 15 randomly attached linker monomers selected from -CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O-(CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, -[C(O)-CH2-O]n-, . , , , , , , , , , , each , n the structure can be included in the Linker as read from left to right or alternatively as read from right to left unless excluded by context. For example, when R15i erBis be . 14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consistin . In certain embodiments, R11, R12, R13, R , R , R , R , R , R , and R are each independently selected from the group consistin . In certain embodiments, at least three of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consistin , . certain embodiments, at least four of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consistin , . In certain embodiments, at least five of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consistin , . er11 12 13 14 15 16 17 18 19 20 tain embodiments, at least six of R , R , R , R , R , R , R , R , R , and R are each independently selected from the group consistin . In certain embodiments, at least seven of R11,20 R are each independently selected from the group consistin , . certain embodiments, at least eight of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consistin , . n certain embodiments, at least nine of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are each independently selected from the group consistin , . In certain embodiments, LinkerBis selected from:

[0024] : ;

[0025] In certain embodiments, LinkerA, LinkerB, LinkerC, or LinkerDis a sequence comprising SEQ ID NO: 81, 82, 83, 84, 85, 86, 87, 88, 89, or 90; or a sequence that has at least 80%, 85%, 90%, 95%, or 98% sequence identity to SEQ ID NO: 81, 82, 83, 84, 85, 86, 87, 88, 89, or 90. SEQ ID NO: 81 SPSTPPTPSPSTPP SEQ ID NO: 82 SPSTPPTPSPSTPPSPSTPP SEQ ID NO: 83 SPTSPPSPTPTSPP SEQ ID NO: 84 PPTSPSPTPPTSPS SEQ ID NO: 85 PPTSPSPTPPTSPSPP SEQ ID NO: 86 SPPSTPSPTPTSPP SEQ ID NO: 87 SPSTPSTPSPSTPP SEQ ID NO: 88 PPTSPSPTPPTSPSSPSTPP SEQ ID NO: 89 PPSTPTPSPPSTPS SEQ ID NO: 90 PPSTPTPSPPSTPSPP In certain embodiments, LinkerA, LinkerB, LinkerC, or LinkerDis an amino acid sequence comprising a peptide that contains between 1 and 10 prolines and optionally between 1 and 10 amino acids selected from serine and threonine. In one embodiment, a divalent residue of a dicarboxylic acid is generated from a nucleophilic addition reaction: . Non-limiting embodiments of a divalent residue oxylic acid generated from a nucleophilic addition reaction include: , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25. As used in the embodiments herein, yy is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25. In one embodiment, a divalent residue of a dicarboxylic acid is generated from a condensation reaction: . Non-limiting embodiments of a divalent residue of a dicarboxylic acid generated from a condensation include: , c acid include: de: on- mtng emo ments o a vaent res ue o a saturate monocaroxy c acid is selected from butyric acid (-OC(O)(CH2)2CH2-), caproic acid (-OC(O)(CH2)4CH2-), caprylic acid (-OC(O)(CH2)5CH2-), capric acid (-OC(O)(CH2)8CH2-), lauric acid (-OC(O)(CH2)10CH2-), myristic acid (-OC(O)(CH2)12CH2-), pentadecanoic acid (-OC(O)(CH2)13CH2-), palmitic acid (-OC(O)(CH2)14CH2-), stearic acid (-OC(O)(CH2)16CH2-), behenic acid (-OC(O)(CH2)20CH2-), and lignoceric acid (-OC(O)(CH2)22CH2-). Non-limiting embodiments of a divalent residue of a fatty acid include residues selected from linoleic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, gadoleic acid, nervonic acid, myristoleic acid, and erucic acid: , Non-limiting embodiments of a divalent residue of a fatty acid is selected from linoleic acid (-C(O)(CH2)7(CH)2CH2(CH)2(CH2)4CH2-), docosahexaenoic acid (–C(O)(CH2)2(CHCHCH2)6CH2-), eicosapentaenoic acid (-C(O)(CH2)3(CHCHCH2)5CH2-), alpha-linolenic acid (–C(O)(CH2)7(CHCHCH2)3CH2-) stearidonic acid (-C(O)(CH2)4(CHCHCH2)4CH2-), y-linolenic acid (-C(O)(CH2)4(CHCHCH2)3(CH2)3CH2-), arachidonic acid (-C(O)(CH2)3,(CHCHCH2)4(CH2)4CH2-), docosatetraenoic acid (-C(O)(CH2)5(CHCHCH2)4(CH2)4CH2-), palmitoleic acid (-C(O)(CH2)7CHCH(CH2)5CH2-), vaccenic acid (-C(O)(CH2)9CHCH(CH2)5CH2-), paullinic acid (-C(O)(CH2)11CHCH(CH2)5CH2-), oleic acid (-C(O)(CH2)7CHCH(CH2)7CH2-), elaidic acid (-C(O)(CH2)7CHCH(CH2)7CH2-), gondoic acid (-C(O)(CH2)9CHCH(CH2)7CH2-), gadoleic acid (- C(O)(CH2)7CHCH(CH2)9CH2-), nervonic acid (-C(O)(CH2)13CHCH(CH2)7CH2-), mead acid (- C(O)(CH2)3(CHCHCH2)3(CH2)6CH2-), myristoleic acid (-C(O)(CH2)7CHCH(CH2)3CH2-), and erucic acid (-C(O)(CH2)11CHCH(CH2)7CH2-). In certain embodiments LinkerCis selected from: . wherein: R22is independently at each occurrence selected from the group consisting of alkyl, -C(O)N-, -NC(O)-, -N-, -C(R21)-, -P(O)O-, -P(O)-, -P(O)(NR6R7)N-, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; and the remaining variables are as defined herein. In certain embodiments LinkerDis selected from: ; wherein: R32is independently at each occurrence selected from the group consisting of alkyl, N+X-, -C-, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; X- is an anionic group, for example Br- or Cl-;and all other variables are as defined herein. In certain embodiments, R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, R16, R17, R18, R19, and R20are bond. In certain embodiments, R17, R18, R19, and R20are bond. In certain embodiments, R18, R19, and R20are bond. In certain embodiments, nine of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, eight of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, seven of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, six of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, five of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, four of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, three of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, two of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond. In certain embodiments, one of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20is bond. In certain embodiments, LinkerAis nd ; wherein each h , 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl. In certain embodiments, R11, R12, R13, R15, R16, R18, R19, and R20are independently selected from bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, - C(R21R21)-, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, and -CH2CH2-[O- (CH2)2]n-O-. In certain embodiments, LinkerAis selected from nd . In certain emb ted from bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, and -CH2CH2-[O-(CH2)2]n-O-. In certain embodiments, R11is selected from the group consisting of bond, CH2, -O-, - C(O)NR6- and -C(O)O-. In certain embodiments, R20is selected from the group consisting of bond, CH2, -O-, -C(O)NR6- and -C(O)O-. In certain embodiments, LinkerAis selected from and . In certain embod bond, CH2, -O-, -C(O)NR6- and -C(O)O-. In certain embodiments, R19is selected from the group consisting of bond, CH2, -O-, -C(O)NR6- and -C(O)O-. In certain embodiments, LinkerAis selected from nd . In certain embodiments, R13is selected from the group consisting of bond, CH2, -O-, -C(O)NR6- and -C(O)O-. In certain embodiments, R18is selected from the group consisting of bond, CH2, -O-, -C(O)NR6- and -C(O)O-. In certain embodiments, aryl is phenyl. In certain embodiments, heterocycle is selected fro . In certain embodiments, LinkerAis selected from , I . ed from . In certain embodiments, LinkerBis: ; wherein: R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are independently at each occurrence selected from the group consisting of a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO2-, -S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, -P(O)(R3)O-, -P(O)(R3)-, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, -CH2CH2-[O-(CH2)2]n-O-, and -CH2CH2-[O-(CH2)2]n-NR6-; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; n is independently selected at each instance from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, hydroxyl, alkoxy, azide, amino, cyano, -NR6R7, -NR8SO2R3, -NR8S(O)R3, haloalkyl, aryl, heteroaryl, and heterocycle. In certain embodiments of LinkerB, R11, R12, R13, R14, R15, R16, and R17are bond. In certain embodiments of LinkerB, five of R11, R12, R13, R14, R15, R16, R17, R18, and R19are bond. In certain embodiments of LinkerB, four of R11, R12, R13, R14, R15, R16, R17, R18, and R19are bond. In certain embodiments of LinkerB, three of R11, R12, R13, R14, R15, R16, R17, R18, and R19are bond. In certain embodiments of LinkerB, R18, R19, and R20are independently selected from bond, alkyl, -C(O)-, - C(O)O-, -OC(O)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, and -CH2CH2-[O-(CH2)2]n-O-. Additional embodiments of LinkerAIn the embodiments of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20provided herein the structure can be included in the Linker as read from left to right or alternatively as read from right to left unless excluded by context. For example, when R15i erAis A be A1. In certain embodiments of LinkerA, R11is bond. A2. In certain embodiments of LinkerA, R11is alkyl. A3. In certain embodiments of LinkerA, R11is -C(O)-. A4. In certain embodiments of LinkerA, R11is -C(O)O-. A5. In certain embodiments of LinkerA, R11is -C(O)NR6-. A6. In certain embodiments of LinkerA, R11is -NR6C(O)-. A7. In certain embodiments of LinkerA, R11is -NR6-. A8. In certain embodiments of LinkerA, R11is -O-. A9. In certain embodiments of LinkerA, R11is -C(R21R21)-. A10. The LinkerAof embodiment A9, wherein both R21groups are hydrogen. A11. In certain embodiments of LinkerA, R11is -CH2CH2-[O-(CH2)2]n-O-. A12. In certain embodiments of LinkerA, R11is aryl. A13. The LinkerAof embodiment A12, wherein R11is phenyl. A14. The LinkerAof embodiment A12, wherein R11is naphthyl. A15. In certain embodiments of LinkerA, R11is heterocycle. A16. The LinkerAof embodiment A15, wherein R11is piperidinyl. A17. The LinkerAof embodiment A16, wherein R11. A18. The LinkerAof embodiment A16, wherei . A19. The LinkerAof embodiment A15, wherei A20. The LinkerAof embodiment A19, wherein R11. A21. The LinkerAof embodiment A15, wherein R11 yl.A22. The LinkerA of embodiment A21, wherei . A23. The LinkerA of embodiment A21, wherei .A24. In certain embodiments of LinkerA, R11i A25. The LinkerAof embodiment A24, wherein R11is pyridinyl. A26. The LinkerAof embodiment A25, wherei . A27. The LinkerAof embodiment A25, wherei . A28. The LinkerAof embodiment A25, wherein R11. A29. The LinkerAof embodiment A24, wherein R11is pyrimidinyl. A30. The LinkerAof embodiment A29, wherein R11. A31. The LinkerAof embodiment A29, wherei . A32. The LinkerAof embodiment A24, wherei . A33. The LinkerAof embodiment A32, wherei . A34. The LinkerAof embodiment A32, wherei . A35. The LinkerAof embodiment A24, wherei A36. The LinkerAof embodiment A35, wherei . A37. The LinkerAof embodiment A35, wherei . A38. In certain embodiments of LinkerA, R11i A39. In certain embodiments of LinkerA, R11is alkoxy. A40. The LinkerAof any one of embodiments A1-A39, wherein R12is bond. A41. The LinkerAof any one of embodiments A1-A39, wherein R12is alkyl. A42. The LinkerAof any one of embodiments A1-A39, wherein R12is -C(O)-. A43. The LinkerAof any one of embodiments A1-A39, wherein R12is -C(O)O-. A44. The LinkerAof any one of embodiments A1-A39, wherein R12is -C(O)NR6-. A45. The LinkerAof any one of embodiments A1-A39, wherein R12is -NR6C(O)-. A46. The LinkerAof any one of embodiments A1-A39, wherein R12is -C(R21R21)-. A47. The LinkerA of embodiment A46, wherein both R21groups are hydrogen. A48. The LinkerAof any one of embodiments A1-A39, wherein R12is -CH2CH2-[O- (CH2)2]n-O-. A49. The LinkerAof any one of embodiments A1-A39, wherein R12is aryl. A50. The LinkerAof embodiment A39, wherein R12is phenyl. A51. The LinkerAof embodiment A39, wherein R12is naphthyl. A52. The LinkerAof any one of embodiments A1-A39, wherein R12is heterocycle. A53. The LinkerAof embodiment A52, wherein R12is piperidinyl. A54. The LinkerAof embodiment A53, wherein R12. A55. The LinkerAof embodiment A53, wherei . A56. The LinkerAof embodiment A52, wherei A57. The LinkerAof embodiment A56, wherein R12i . A58. The LinkerAof embodiment A52, wherein R12i yl.A59. The LinkerA of embodiment A58, wherei . A60. The LinkerA of embodiment A59, wherei .A61. The LinkerAof any one of embodiments - , w e e R12is heteroaryl. A62. The LinkerAof embodiment A61, wherein R12is pyridinyl. A63. The LinkerAof embodiment A62, wherei . A64. The LinkerAof embodiment A62, wherei . A65. The LinkerAof embodiment A62, wherein R12. A66. The LinkerAof embodiment A61, wherein R12 A67. The LinkerAof embodiment A66, wherein R12. A68. The LinkerAof embodiment A66, wherei . A69. The LinkerAof embodiment A61, wherei . A70. The LinkerAof embodiment A69, wherei . A71. The LinkerAof embodiment A68, wherei . A72. The LinkerAof embodiment A61, wherei . A73. The LinkerAof embodiment A72, wherei . A74. The LinkerAof embodiment A72, wherei . A75. The LinkerAof any one of embodiments alkynyl. A76. The LinkerAof any one of embodiments A1-A39, wherein R12is alkoxy. A77. The LinkerAof any one of embodiments A1-A76, wherein R13is bond. A78. The LinkerAof any one of embodiments A1-A76, wherein R13is alkyl. A79. The LinkerAof any one of embodiments A1-A76, wherein R13is -C(O)-. A80. The LinkerAof any one of embodiments A1-A76, wherein R13is -C(O)O-. A81. The LinkerAof any one of embodiments A1-A76, wherein R13is -C(O)NR6-. A82. The LinkerAof any one of embodiments A1-A76, wherein R13is -NR6C(O)-. A83. The LinkerAof any one of embodiments A1-A76, wherein R13is -NR6-. A84. The LinkerAof any one of embodiments A1-A76, wherein R13is -O-. A85. The LinkerAof any one of embodiments A1-A76, wherein R13is -C(R21R21)-. A86. The LinkerA of embodiment A85, wherein both R21groups are hydrogen. A87. The LinkerAof any one of embodiments A1-A76, wherein R13is -CH2CH2-[O- (CH2)2]n-O-. A88. The LinkerAof any one of embodiments A1-A76, wherein R13is aryl. A89. The LinkerAof embodiment A88, wherein R13is phenyl. A90. The LinkerAof embodiment A88, wherein R13is naphthyl. A91. The LinkerAof any one of embodiments A1-A76, wherein R13is heterocycle. A92. The LinkerAof embodiment A91, wherein R13is piperidinyl. A93. The LinkerAof embodiment A92, wherein R13i . A94. The LinkerAof embodiment A92, wherei . A95. The LinkerAof embodiment A91, wherei s ppe y . A96. The LinkerAof embodiment A95, wherein R13is . A97. The LinkerAof embodiment A91, wherein R13l. A98. The LinkerA of embodiment A97, wherei . A99. The LinkerA of embodiment A97, wherei .A100. The LinkerAof any one of embodiments13 R is heteroaryl. A101. The LinkerAof embodiment A100, wherein R13is pyridinyl. A102. The LinkerAof embodiment A101, wherei . A103. The LinkerAof embodiment A101, wherei . A104. The LinkerAof embodiment A101, wherein R13. A105. The LinkerAof embodiment A100, wherein R13 py y . A106. The LinkerAof embodiment A105, wherein R13. A107. The LinkerAof embodiment A105, wherei . A108. The LinkerAof embodiment A100, wherein R13is pyrazinyl. A109. The LinkerAof embodiment A108, wherei . A110. The LinkerAof embodiment A108, wherei . A111. The LinkerAof embodiment A100, wherei A112. The LinkerAof embodiment A111, wherein R13is . A113. The LinkerAof embodiment A111, wherei . A114. The LinkerAof any one of embodiments A kynyl. A115. The LinkerAof any one of embodiments A1-A76, wherein R13is alkoxy. A116. The LinkerAof any one of embodiments A1-A115, wherein R14is bond. A117. The LinkerAof any one of embodiments A1-A115, wherein R14is alkyl. A118. The LinkerAof any one of embodiments A1-A115, wherein R14is -C(O)-. A119. The LinkerAof any one of embodiments A1-A115, wherein R14is -C(O)O-. A120. The LinkerAof any one of embodiments A1-A115, wherein R14is -C(O)NR6-. A121. The LinkerAof any one of embodiments A1-A115, wherein R14is -NR6C(O)-. A122. The LinkerAof any one of embodiments A1-A115, wherein R14is -S(O)-. A123. The LinkerAof any one of embodiments A1-A115, wherein R14is –S(O)2-. A124. The LinkerAof any one of embodiments A1-A115, wherein R14is -C(R21R21)-. A125. The LinkerA of embodiment A124, wherein both R21groups are hydrogen. A126. The LinkerAof any one of embodiments A1-A115, wherein R14is -CH2CH2-[O- (CH2)2]n-O-. A127. The LinkerAof any one of embodiments A1-A115, wherein R14is aryl. A128. The LinkerAof embodiment A127, wherein R14is phenyl. A129. The LinkerAof embodiment A127, wherein R14is naphthyl. A130. The LinkerAof any one of embodiments A1-A115, wherein R14is heterocycle. A131. The LinkerAof embodiment A130, wherein R14is piperidinyl. A132. The LinkerAof embodiment A131, wherein R14i . A133. The LinkerAof embodiment A131, wherei . A134. The LinkerAof embodiment A130, wherei l. A135. The LinkerAof embodiment A134, wherein R14i . A136. The LinkerAof embodiment A130, wherein R14i yl.A137. The LinkerA of embodiment A136, wherei . A138. The LinkerA of embodiment A136, wherei .A139. The LinkerAof any one of embodiments A R14is heteroaryl. A140. The LinkerAof embodiment A139, wherein R14is pyridinyl. A141. The LinkerAof embodiment A140, wherei . A142. The LinkerAof embodiment A140, wherei . A143. The LinkerAof embodiment A140, wherein R14. A144. The LinkerAof embodiment A139, wherein R14 A145. The LinkerAof embodiment A144, wherein R14. A146. The LinkerAof embodiment A144, wherei . A147. The LinkerAof embodiment A139, wherei A148. The LinkerAof embodiment A147, wherei . A149. The LinkerAof embodiment A147, wherei . A150. The LinkerAof embodiment A139, wherei A151. The LinkerAof embodiment A150, wherei . A152. The LinkerAof embodiment A150, wherei . A153. The LinkerAof any one of embodiments A , lkynyl. A154. The LinkerAof any one of embodiments A1-A115, wherein R14is alkoxy. A155. The LinkerAof any one of embodiments A1-A154, wherein R15is bond. A156. The LinkerAof any one of embodiments A1-A154, wherein R15is alkyl. A157. The LinkerAof any one of embodiments A1-A154, wherein R15is -C(O)-. A158. The LinkerAof any one of embodiments A1-A154, wherein R15is -C(O)O-. A159. The LinkerAof any one of embodiments A1-A154, wherein R15is -C(O)NR6-. A160. The LinkerAof any one of embodiments A1-A154, wherein R15is -NR6C(O)-. A161. The LinkerAof any one of embodiments A1-A154, wherein R15is -NR6-. A162. The LinkerAof any one of embodiments A1-A154, wherein R15is -O-. A163. The LinkerAof any one of embodiments A1-A154, wherein R15is -C(R21R21)-. A164. The LinkerA of embodiment A163, wherein both R21groups are hydrogen. A165. The LinkerAof any one of embodiments A1-A154, wherein R15is -CH2CH2-[O- (CH2)2]n-O-. A166. The LinkerAof any one of embodiments A1-A154, wherein R15is aryl. A167. The LinkerAof embodiment A166, wherein R15is phenyl. A168. The LinkerAof embodiment A166, wherein R15is naphthyl. A169. The LinkerAof any one of embodiments A1-A154, wherein R15is heterocycle. A170. The LinkerAof embodiment A169, wherein R15is piperidinyl. A171. The LinkerAof embodiment A170, wherein R15. A172. The LinkerAof embodiment A170, wherei . A173. The LinkerAof embodiment A169, wherei A174. The LinkerAof embodiment A173, wherein R15i . A175. The LinkerAof embodiment A169, wherein R15i y yl.A176. The LinkerA of embodiment A175, wherei . A177. The LinkerA of embodiment A175, wherei .A178. The LinkerAof any one of embodiments A R15is heteroaryl. A179. The LinkerAof embodiment A178, wherein R15is pyridinyl. A180. The LinkerAof embodiment A179, wherei . A181. The LinkerAof embodiment A179, wherei . A182. The LinkerAof embodiment A179, wherein R15. A183. The LinkerAof embodiment A178, wherein R15 A184. The LinkerAof embodiment A183, wherein R15. A185. The LinkerAof embodiment A183, wherei . A186. The LinkerAof embodiment A178, wherei . A187. The LinkerAof embodiment A186, wherei . A188. The LinkerAof embodiment A186, wherei . A189. The LinkerAof embodiment A178, wherein R15is pyridizinyl. A190. The LinkerAof embodiment A189, wherei . A191. The LinkerAof embodiment A189, wherei . A192. The LinkerAof any one of embodiments A lkynyl. A193. The LinkerAof any one of embodiments A1-A154, wherein R15is alkoxy. A194. The LinkerAof any one of embodiments A1-A193, wherein R16is bond. A195. The LinkerAof any one of embodiments A1-A193, wherein R16is alkyl. A196. The LinkerAof any one of embodiments A1-A193, wherein R16is -C(O)-. A197. The LinkerAof any one of embodiments A1-A193, wherein R16is -C(O)O-. A198. The LinkerAof any one of embodiments A1-A193, wherein R16is -C(O)NR6-. A199. The LinkerAof any one of embodiments A1-A193, wherein R16is -NR6C(O)-. A200. The LinkerAof any one of embodiments A1-A193, wherein R16is -S(O)-. A201. The LinkerAof any one of embodiments A1-A193, wherein R16is -S(O)2-. A202. The LinkerAof any one of embodiments A1-A193, wherein R16is -C(R21R21)-. A203. The LinkerA of embodiment A202, wherein both R21groups are hydrogen. A204. The LinkerAof any one of embodiments A1-A193, wherein R16is -CH2CH2-[O- (CH2)2]n-O-. A205. The LinkerAof any one of embodiments A1-A193, wherein R16is aryl. A206. The LinkerAof embodiment A205, wherein R16is phenyl. A207. The LinkerAof embodiment A205, wherein R16is naphthyl. A208. The LinkerAof any one of embodiments A1-A193, wherein R16is heterocycle. A209. The LinkerAof embodiment A208, wherein R16is piperidinyl. A210. The LinkerAof embodiment A209, wherein R16. A211. The LinkerAof embodiment A209, wherei . A212. The LinkerAof embodiment A208, wherei l. A213. The LinkerAof embodiment A212, wherein R16i . A214. The LinkerAof embodiment A208, wherein R16i yl.A215. The LinkerA of embodiment A214, wherein R16 is .A216. The LinkerA of embodiment A214, wherei .A217. The LinkerAof any one of embodiments A16 R is heteroaryl. A218. The LinkerAof embodiment A217, wherein R16is pyridinyl. A219. The LinkerAof embodiment A218, wherei . A220. The LinkerAof embodiment A218, wherei . A221. The LinkerAof embodiment A218, wherein R16. A222. The LinkerAof embodiment A217, wherein R16 is pyrimidinyl. A223. The LinkerAof embodiment A222, wherein R16. A224. The LinkerAof embodiment A222, wherei . A225. The LinkerAof embodiment A217, wherei . A226. The LinkerAof embodiment A225, wherei . A227. The LinkerAof embodiment A225, wherei . A228. The LinkerAof embodiment A217, wherei A229. The LinkerAof embodiment A228, wherei . A230. The LinkerAof embodiment A228, wherei . A231. The LinkerAof any one of embodiments A lkynyl. A232. The LinkerAof any one of embodiments A1-A193, wherein R16is alkoxy. A233. The LinkerAof any one of embodiments A1-A232, wherein R17is bond. A234. The LinkerAof any one of embodiments A1-A232, wherein R17is alkyl. A235. The LinkerAof any one of embodiments A1-A232, wherein R17is -C(O)-. A236. The LinkerAof any one of embodiments A1-A232, wherein R17is -C(O)O-. A237. The LinkerAof any one of embodiments A1-A232, wherein R17is -C(O)NR6-. A238. The LinkerAof any one of embodiments A1-A232, wherein R17is -NR6C(O)-. A239. The LinkerAof any one of embodiments A1-A232, wherein R17is -NR6-. A240. The LinkerAof any one of embodiments A1-A232, wherein R17is -O-. A241. The LinkerAof any one of embodiments A1-A232, wherein R17is -C(R21R21)-. A242. The LinkerA of embodiment A241, wherein both R21groups are hydrogen. A243. The LinkerAof any one of embodiments A1-A232, wherein R17is -CH2CH2-[O- (CH2)2]n-O-. A244. The LinkerAof any one of embodiments A1-A232, wherein R17is aryl. A245. The LinkerAof embodiment A244, wherein R17is phenyl. A246. The LinkerAof embodiment A244, wherein R17is naphthyl. A247. The LinkerAof any one of embodiments A1-A232, wherein R17is heterocycle. A248. The LinkerAof embodiment A247, wherein R17is piperidinyl. A249. The LinkerAof embodiment A248, wherein R17. A250. The LinkerAof embodiment A248, wherei . A251. The LinkerAof embodiment A247, wherei l. A252. The LinkerAof embodiment A251, wherein R17i . A253. The LinkerAof embodiment A247, wherein R17i yl.A254. The LinkerA of embodiment A253, wherein R17 is .A255. The LinkerA of embodiment A253, wherei .A256. The LinkerAof any one of embodiments A , R17is heteroaryl. A257. The LinkerAof embodiment A256, wherein R17is pyridinyl. A258. The LinkerAof embodiment A257, wherein R17is . A259. The LinkerAof embodiment A257, wherei . A260. The LinkerAof embodiment A257, wherein R17. A261. The LinkerAof embodiment A256, wherein R17 A262. The LinkerAof embodiment A261, wherein R17. A263. The LinkerAof embodiment A261, wherei . A264. The LinkerAof embodiment A256, wherei A265. The LinkerAof embodiment A264, wherein R17is . A266. The LinkerAof embodiment A264, wherei . A267. The LinkerAof embodiment A256, wherei A268. The LinkerAof embodiment A267, wherei . A269. The LinkerAof embodiment A267, wherei . A270. The LinkerAof any one of embodiments A - , w ere n s alkynyl. A271. The LinkerAof any one of embodiments A1-A232, wherein R17is alkoxy. A272. The LinkerAof any one of embodiments A1-A271, wherein R18is bond. A273. The LinkerAof any one of embodiments A1-A271, wherein R18is alkyl. A274. The LinkerAof any one of embodiments A1-A271, wherein R18is -C(O)-. A275. The LinkerAof any one of embodiments A1-A271, wherein R18is -C(O)O-. A276. The LinkerAof any one of embodiments A1-A271, wherein R18is -C(O)NR6-. A277. The LinkerAof any one of embodiments A1-A271, wherein R18is -NR6C(O)-. A278. The LinkerAof any one of embodiments A1-A271, wherein R18is -S(O)-. A279. The LinkerAof any one of embodiments A1-A271, wherein R18is -S(O)2-. A280. The LinkerAof any one of embodiments A1-A271, wherein R18is -C(R21R21)-. A281. The LinkerA of embodiment A280, wherein both R21groups are hydrogen. A282. The LinkerAof any one of embodiments A1-A271, wherein R18is -CH2CH2-[O- (CH2)2]n-O-. A283. The LinkerAof any one of embodiments A1-A271, wherein R18is aryl. A284. The LinkerAof embodiment A283, wherein R18is phenyl. A285. The LinkerAof embodiment A283, wherein R18is naphthyl. A286. The LinkerAof any one of embodiments A1-A271, wherein R18is heterocycle. A287. The LinkerAof embodiment A286, wherein R18is piperidinyl. A288. The LinkerAof embodiment A287, wherein R18. A289. The LinkerAof embodiment A287, wherei . A290. The LinkerAof embodiment A286, wherei l. A291. The LinkerAof embodiment A290, wherein R18. A292. The LinkerAof embodiment A286, wherein R18 s pyrro d nyl.A293. The LinkerA of embodiment A292, wherei . A294. The LinkerA of embodiment A292, wherei .A295. The LinkerAof any one of embodiments A R18is heteroaryl. A296. The LinkerAof embodiment A295, wherein R18is pyridinyl. A297. The LinkerAof embodiment A296, wherei . A298. The LinkerAof embodiment A296, wherei . A299. The LinkerAof embodiment A296, wherein R18. A300. The LinkerAof embodiment A295, wherein R18 A301. The LinkerAof embodiment A300, wherein R18. A302. The LinkerAof embodiment A300, wherei . A303. The LinkerAof embodiment A295, wherei py y . A304. The LinkerAof embodiment A303, wherei . A305. The LinkerAof embodiment A303, wherein R18is . A306. The LinkerAof embodiment A295, wherein R18is pyridizinyl. A307. The LinkerAof embodiment A306, wherei . A308. The LinkerAof embodiment A306, wherei . A309. The LinkerAof any one of embodiments A lkynyl. A310. The LinkerAof any one of embodiments A1-A271, wherein R18is alkoxy. A311. The LinkerAof any one of embodiments A1-A310, wherein R19is bond. A312. The LinkerAof any one of embodiments A1-A310, wherein R19is alkyl. A313. The LinkerAof any one of embodiments A1-A310, wherein R19is -C(O)-. A314. The LinkerAof any one of embodiments A1-A310, wherein R19is -C(O)O-. A315. The LinkerAof any one of embodiments A1-A310, wherein R19is -C(O)NR6-. A316. The LinkerAof any one of embodiments A1-A310, wherein R19is -NR6C(O)-. A317. The LinkerAof any one of embodiments A1-A310, wherein R19is -NR6-. A318. The LinkerAof any one of embodiments A1-A310, wherein R19is -O-. A319. The LinkerAof any one of embodiments A1-A310, wherein R19is -C(R21R21)-. A320. The LinkerA of embodiment A319, wherein both R21groups are hydrogen. A321. The LinkerAof any one of embodiments A1-A310, wherein R19is -CH2CH2-[O- (CH2)2]n-O-. A322. The LinkerAof any one of embodiments A1-A310, wherein R19is aryl. A323. The LinkerAof embodiment A322, wherein R19is phenyl. A324. The LinkerAof embodiment A322, wherein R19is naphthyl. A325. The LinkerAof any one of embodiments A1-A310, wherein R19is heterocycle. A326. The LinkerAof embodiment A325, wherein R19is piperidinyl. A327. The LinkerAof embodiment A326, wherein R19i . A328. The LinkerAof embodiment A326, wherei . A329. The LinkerAof embodiment A325, wherei A330. The LinkerAof embodiment A329, wherein R19i . A331. The LinkerAof embodiment A325, wherein R19i yl.A332. The LinkerA of embodiment A331, wherei . A333. The LinkerA of embodiment A331, wherei .A334. The LinkerAof any one of embodiments A R19is heteroaryl. A335. The LinkerAof embodiment A334, wherein R19is pyridinyl. A336. The LinkerAof embodiment A335, wherei . A337. The LinkerAof embodiment A335, wherei . A338. The LinkerAof embodiment A335, wherein R19. A339. The LinkerAof embodiment A334, wherein R19 A340. The LinkerAof embodiment A339, wherein R19. A341. The LinkerAof embodiment A339, wherei . A342. The LinkerAof embodiment A334, wherei A343. The LinkerAof embodiment A342, wherei . A344. The LinkerAof embodiment A342, wherei . A345. The LinkerAof embodiment A334, wherei A346. The LinkerAof embodiment A345, wherei . A347. The LinkerAof embodiment A345, wherei . A348. The LinkerAof any one of embodiments A , lkynyl. A349. The LinkerAof any one of embodiments A1-A310, wherein R19is alkoxy. A350. The LinkerAof any one of embodiments A1-A349, wherein R20is bond. A351. The LinkerAof any one of embodiments A1-A349, wherein R20is alkyl. A352. The LinkerAof any one of embodiments A1-A349, wherein R20is -C(O)-. A353. The LinkerAof any one of embodiments A1-A349, wherein R20is -C(O)O-. A354. The LinkerAof any one of embodiments A1-A349, wherein R20is -C(O)NR6-. A355. The LinkerAof any one of embodiments A1-A349, wherein R20is -NR6C(O)-. A356. The LinkerAof any one of embodiments A1-A349, wherein R20is -S(O)-. A357. The LinkerAof any one of embodiments A1-A349, wherein R20is -S(O)2-. A358. The LinkerAof any one of embodiments A1-A349, wherein R20is -C(R21R21)-. A359. The LinkerA of embodiment A358, wherein both R21groups are hydrogen. A360. The LinkerAof any one of embodiments A1-A349, wherein R20is -CH2CH2-[O- (CH2)2]n-O-. A361. The LinkerAof any one of embodiments A1-A349, wherein R20is aryl. A362. The LinkerAof embodiment A361, wherein R20is phenyl. A363. The LinkerAof embodiment A361, wherein R20is naphthyl. A364. The LinkerAof any one of embodiments A1-A349, wherein R20is heterocycle. A365. The LinkerAof embodiment A364, wherein R20is piperidinyl. A366. The LinkerAof embodiment A364, wherein R20i . A367. The LinkerAof embodiment A364, wherei . A368. The LinkerAof embodiment A364, wherei A369. The LinkerAof embodiment A364, wherein R20i . A370. The LinkerAof embodiment A364, wherein R20i y yl.A371. The LinkerA of embodiment A364, wherei . A372. The LinkerA of embodiment A364, wherei .A373. The LinkerAof any one of embodiments A R20is heteroaryl. A374. The LinkerAof embodiment A373, wherein R20is pyridinyl. A375. The LinkerAof embodiment A373, wherei . A376. The LinkerAof embodiment A373, wherei . A377. The LinkerAof embodiment A373, wherein R20. A378. The LinkerAof embodiment A373, wherein R20 A379. The LinkerAof embodiment A373, wherein R20. A380. The LinkerAof embodiment A373, wherei . A381. The LinkerAof embodiment A373, wherei . A382. The LinkerAof embodiment A373, wherei . A383. The LinkerAof embodiment A373, wherei . A384. The LinkerAof embodiment A373, wherein R20is pyridizinyl. A385. The LinkerAof embodiment A373, wherei . A386. The LinkerAof embodiment A373, wherei . A387. The LinkerAof any one of embodiments A lkynyl. A388. The LinkerAof any one of embodiments A1-A349, wherein R20is alkoxy. A389. The LinkerAof any one of embodiments A1-A388, wherein R11, R12, R13, R14, R15, R16, R17, R18, R19, or R20is substituted with two R21substituents, wherein the substituents are selected such that a stable compound results. A390. The LinkerAof any one of embodiments A1-A388, wherein R11, R12, R13, R14, R15, R16, R17, R18, R19, or R20is substituted with three R21substituents, wherein the substituents are selected such that a stable compound results. A391. The LinkerAof any one of embodiments A1-A388, wherein R11, R12, R13, R14, R15, R16, R17, R18, R19, or R20is substituted with four R21substituents, wherein the substituents are selected such that a stable compound results. A392. The LinkerAof any one of embodiments A1-A388, wherein R11, R12, R13, R14, R15, R16, R17, R18, R19, or R20is substituted with one R21substituent. A393. The LinkerAof any one of embodiments A1-A392, wherein R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, hydroxyl, alkoxy, amino, -NR6R7, haloalkyl, aryl, heteroaryl, and heterocycle. A394. The LinkerAof any one of embodiments A1-A393, R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, F, hydroxyl, alkoxy, amino, -NR6R7, haloalkyl, aryl, heteroaryl, and heterocycle. A395. The LinkerAof any one of embodiments A1-A394, R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, F, hydroxyl, alkoxy, amino, -NR6R7, and haloalkyl. A396. The LinkerAof any one of embodiments A1-A391, wherein one of the R21groups is hydrogen. A397. The LinkerAof any one of embodiments A1-A391, wherein one of the R21groups is fluorine. A398. The LinkerAof any one of embodiments A1-A391, wherein one of the R21groups is alkyl. A399. The LinkerAof embodiment A398, wherein one of the R21groups is methyl. A400. The LinkerAof embodiment A398, wherein one of the R21groups is ethyl. A401. The LinkerAof embodiment A398, wherein one of the R21groups is isopropyl. A402. The LinkerAof any one of embodiments A1-A391, wherein one of the R21groups is hydroxyl. A403. The LinkerAof any one of embodiments A1-A391, wherein one of the R21groups is -NR6R7. A404. The LinkerAof embodiment A403, wherein one of the R21groups is dimethylamino. A405. The LinkerAof any one of embodiments A1-A391 and A393-A398, wherein a second R21group is hydrogen. A406. The LinkerAof any one of embodiments A1-A391 and A393-A398, wherein a second R21group is fluorine. A407. The LinkerAof any one of embodiments A1-A391 and A393-A398, wherein a second R21group is alkyl. A408. The LinkerAof any one of embodiments A1-A388 and A390-A391, wherein a third R21is hydrogen. A409. The LinkerAof any one of embodiments A1-A388 and A390-A391, wherein a third R21is fluorine. A410. The LinkerAof any one of embodiments A1-A388 and A390-A391, wherein a third R21is alkyl. A411. The LinkerAof any one of embodiments A1-A388 and A391, wherein a fourth R21is hydrogen In certain embodiments LinkerAis selected from: erein. In certain embodiments LinkerAis selected from: each of which is optiona with 1, 2, 3, or tional substituents as defin erein. In certain embodiments LinkerAis selected from: each of which is optiona y d with 1, 2 , , ptional substituents as defin erein. In certain embodiments LinkerAis selected from: each of which is optiona lly substituted with 1, 2, 3, or 4 optional substituents as defin ed herein. In certain embodiments LinkerAis selected from: and each of ted with 1, 2, 3, or 4 optional substituents as defined herein. In certain embodiments LinkerAis selected from: ; be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments LinkerAis selected from: ; be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments LinkerAis selected from:

[0026] ; tituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments LinkerBis selected from: . In certain embodiments LinkerB, LinkerC, or LinkerDis selected from:

[0027] nd wherein each heteroaryl, heterocycle, cycloalkyl, and aryl can optionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence; and tt and ss are as defined herein. In certain embodiments LinkerB, LinkerC, or LinkerDis selected from: nd ith 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence; and tt and ss are as defined herein. In certain embodiments LinkerAis selected from: , , , ein. In certain embodiments LinkerCis selected from: nd In certain embodiments, the LinkerAis selected from n certan emo ments ner s seecte rom: . In certain embodiments LinkerAis selected from: nd , , . ents LinkerB-LinkerAis selected from: . nd nd n certan embodments, ner s seected rom . , , In certain embodiments LinkerC-(LinkerA)2is selected from: . In certain embodiments, the LinkerDis selected from nd . n ceran emo mens, ner-( ner) s seece rom

[0028] nd In certain embodiments, LinkerD-(LinkerA) is selected from . In certain embodiments LinkerBis selected from: ted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments LinkerBis selected from: th 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments LinkerBis selected from: ; ptionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments, LinkerBis nd ; where , , , , 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl. In certain embodiments, LinkerBis selected from d . In certain embodiments LinkerB, LinkerC, or LinkerDis selected from: wherein each heteroaryl, heterocycle, cycloalkyl, and aryl can optionally be substituted with 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl, as allowed by valence. In certain embodiments LinkerAis selected from: , p . bodiA ments Linker is bond. In certain embodiments the left side of LinkerAis attached to the ASGPR Binding Ligand and the right side is attached to LinkerB, LinkerC, or LinkerD. In certain embodiments the right side of LinkerAis attached to the ASGPR Binding Ligand and the right side is attached to LinkerB, LinkerC, or LinkerD. In certain embodiments LinkerBis selected from: , . . tached to the Extracellular Targeting Ligand and the right side is attached to LinkerA. In certain embodiments the right side of LinkerBis attached to the Extracellular Targeting Ligand and the left side is attached to LinkerA. In certain embodiments LinkerBis bond. In alternative embodiments a linker is provided as described above wherein is replaced with a , for example where LinkerBis draw in this embodim . In alternative embodiments a linker is provided as described above wherein a is replaced with a , for example where LinkerBis drawn as in t s em o men . In alternative embodiments a linker is provided as described above wherein a is replaced with a . Additional Embodiments of Linker In certain embodiments, the linker includes at least a linear group comprising groups selected from alkyl, amide, disulfide, polyethylene glycol, ether, thioether (-S-) and hydroxylamino (-O-N(H)-) groups. In certain embodiments, the linear group comprises groups selected from alkyl, amide and ether groups. In certain embodiments, the linear group comprises groups selected from alkyl and ether groups. In certain embodiments, the linear group comprises at least one phosphorus linking group. In certain embodiments, the linear group comprises at least one phosphodiester group. In certain embodiments, the linear group includes at least one neutral linking group. In certain embodiments, LinkerBis selected from:

[0029] wherein each L is independently a phosphorus linking group or a neutral linking group. In certain embodiments, LinkerBis selected from:

[0030] . ce a e o e s, e s seece o : . In certain embodiments, Linker is selected from: nd In certain embodiments, LinkerDis selected from: In certain embodiments n is independently 0, 1, 2, 3, 4, 5, 6, or 7. In certain embodiments n is 1. In certain embodiments n is 2. In certain embodiments n is 3. In certain embodiments n is 4. In certain embodiments n is 5. In certain embodiments n is 6. In certain embodiments n is 7. Embodiments of ASGPR Binding Ligand In certain embodiments ASGPR Binding Ligand is of Formula: . In certain embodiments A of Formula: . In certain embodiments A of Formula: . In certain embodiments A of Formula: . In certain embodiments ASGPR Binding Ligand is of Formula: . In certain embodiments A f Formula: . In certain embodiments A f Formula: . In certain embodiments AS of Formula: . In certain embodiments AS of Formula: . In certain embodiments ASGPR Binding Ligand is of Formula: . In certain embodiments ASGP ormula: . In certain embodiments Formula: . In certain embodiments A f Formula: . In certain embodiments ASGPR Binding Ligand is of Formula: . In certain embodiments ASGPR Binding Ligand is of Formula: . In certain embodiments A of Formula: . In certain embodiments A of Formula: . In certain embodiments AS G nd ng gand s of Formula: . In certain embodiments A of Formula: . In certain embodiments A of Formula: . In certain embodiments A of Formula: . In certain embodiments AS g g of Formula: . In certain embodiments ASGPR Binding Ligand is of Formula: . In certain embodiments A of Formula: . In certain embodiments ASGP ormula: . In certain embodiments Formula: . In certain aspects the apoB degrading compound is of Formula or a pharmaceutically In certain aspects the apoB degrading compound is of Formula or a pharm In certain aspects the apoB degrading compound is of Formula or a pharmaceutically acceptable salt thereof. In certain aspects the apoB degrading compound is of Formula or a pharmaceutica In certain aspects the apoB degrading compound is of Formula or a pharm In certain aspects the apoB degrading compound is of Formula or a pharm aceu ca y accepa e sa eeo. In certain embodiments ASGPR Binding Ligand is of Formula: wherein R* is selected from: and . , . m . In certain embodiments, ASGPR Binding Ligand is selected from

[0031] d In certain embodiments the apoB degrading compound is selected from: Embodiments of R1In certain embodiments R1is hydrogen. In certain embodiments R1is . In certain embodiments R1i . In certain embodiments R1i . In certain embodiments R1i . In certain embodiments R1is . In certain embodiments . In certain embodiments R1is C0-C6alkyl-cyano optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is alkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is alkenyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is alkynyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is haloalkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is F. In certain embodiments R1is Cl. In certain embodiments R1is Br. In certain embodiments R1is aryl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is arylalkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is heteroaryl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is heteroarylalkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is heterocycle optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is heterocycloalkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is haloalkoxy optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R1is -O-alkenyl, -O-alkynyl, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0- C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, or C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, 3, or 4 substituents. Embodiments of R3In certain embodiments R3is hydrogen or alkyl. In certain embodiments R3is hydrogen. In certain embodiments R3is alkyl. In certain embodiments R3is haloalkyl. In certain embodiments R3is arylalkyl. In certain embodiments R3is heteroarylalkyl. In certain embodiments R3is alkenyl. In certain embodiments R3is alkynyl. In certain embodiments R3is aryl. In certain embodiments R3is phenyl. In certain embodiments R3is heteroaryl. In certain embodiments R3is pyridine. In certain embodiments R3is heterocycle. In certain embodiments R3is -OR8. In certain embodiments R3is -OH. In certain embodiments R3is -NR8R9. In certain embodiments R3is -NH2. Embodiments of R5In certain embodiments R5is hydrogen. In certain embodiments R5is . In certain embodiments R5is . In certain embodiments R5is . In certain embodiments R5is . In certain embodiments R5i . In certain embodiments R5is . In certain embodiments R5is C0-C6alkyl-cyano optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is alkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is alkenyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is alkynyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is haloalkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is F. In certain embodiments R5is Cl. In certain embodiments R5is Br. In certain embodiments R5is aryl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is arylalkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is heteroaryl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is heteroarylalkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is heterocycle optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is heterocycloalkyl optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is haloalkoxy optionally substituted with 1, 2, 3, or 4 substituents. In certain embodiments R5is -O-alkenyl, -O-alkynyl, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0- C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, or C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, 3, or 4 substituents. Embodiments of R6and R7In certain embodiments R6and R7are independently selected from hydrogen and alkyl. In certain embodiments R6is C(O)Me and R7is H. In certain embodiments R6is hydrogen. In certain embodiments R6is alkyl. In certain embodiments R6is methyl. In certain embodiments R6is ethyl. In certain embodiments R6is arylalkyl. In certain embodiments R6is benzyl. In certain embodiments R6is heteroarylalkyl. In certain embodiments R6is alkenyl. In certain embodiments R6is alkynyl. In certain embodiments R6is aryl. In certain embodiments R6is phenyl. In certain embodiments R6is arylalkyl. In certain embodiments R6is haloalkyl. In certain embodiments R6is trifluoromethyl. In certain embodiments R6is heteroaryl. In certain embodiments R6is heterocycle. In certain embodiments R6is -alkyl-OR8. In certain embodiments R6is -alkyl-NR8R9. In certain embodiments R6is C(O)R3. In certain embodiments R6is C(O)Me. In certain embodiments R6is S(O)R3. In certain embodiments R6is C(S)R3. In certain embodiments R6is S(O)2R3. In certain embodiments R7is hydrogen. In certain embodiments R7is alkyl. In certain embodiments R7is methyl. In certain embodiments R7is ethyl. In certain embodiments R7is arylalkyl. In certain embodiments R7is benzyl. In certain embodiments R7is heteroarylalkyl. In certain embodiments R7is alkenyl. In certain embodiments R7is alkynyl. In certain embodiments R7is aryl. In certain embodiments R7is phenyl. In certain embodiments R7is arylalkyl. In certain embodiments R7is haloalkyl. In certain embodiments R7is trifluoromethyl. In certain embodiments R7is heteroaryl. In certain embodiments R7is heterocycle. In certain embodiments R7is -alkyl-OR8. In certain embodiments R7is -alkyl-NR8R9. In certain embodiments R7is C(O)R3. In certain embodiments R7is C(O)Me. In certain embodiments R7is S(O)R3. In certain embodiments R7is C(S)R3. In certain embodiments R7is S(O)2R3. Embodiments of R8and R9In certain embodiments R8and R9are independently selected from hydrogen and alkyl. In certain embodiments R8is hydrogen. In certain embodiments R8is alkyl. In certain embodiments R8is methyl. In certain embodiments R8is ethyl. In certain embodiments R8is arylalkyl. In certain embodiments R8is benzyl. In certain embodiments R8is heteroarylalkyl. In certain embodiments R8is alkenyl. In certain embodiments R8is alkynyl. In certain embodiments R8is aryl. In certain embodiments R8is phenyl. In certain embodiments R8is arylalkyl. In certain embodiments R8is haloalkyl. In certain embodiments R8is trifluoromethyl. In certain embodiments R8is heteroaryl. In certain embodiments R8is heterocycle. In certain embodiments R9is hydrogen. In certain embodiments R9is alkyl. In certain embodiments R9is methyl. In certain embodiments R9is ethyl. In certain embodiments R9is arylalkyl. In certain embodiments R9is benzyl. In certain embodiments R9is heteroarylalkyl. In certain embodiments R9is alkenyl. In certain embodiments R9is alkynyl. In certain embodiments R9is aryl. In certain embodiments R9is phenyl. In certain embodiments R9is arylalkyl. In certain embodiments R9is haloalkyl. In certain embodiments R9is trifluoromethyl. In certain embodiments R9is heteroaryl. In certain embodiments R9is heterocycle. Embodiments of R10In certain embodiments R10is hydrogen. In certain embodiments R10is alkyl. In certain embodiments R10is haloalkyl. In certain embodiments R10is C(O)R3. Embodiments of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20In certain embodiments R11is bond. In certain embodiments R11is alkyl. In certain embodiments R11is C(O). In certain embodiments R11is -C(O)O-. In certain embodiments R11is -C(O)NR6-. In certain embodiments R11is -O-. In certain embodiments R11is -NR6-. In certain embodiments R11is a divalent residue of a natural amino acid. In certain embodiments R11is a divalent residue of an unnatural amino acid. In certain embodiments R11is -CH2CH2-[O-(CH2)2]n-O-. In certain embodiments R11is -CH2CH2-[O-(CH2)2]n-NR6-. In certain embodiments R11is -CH2CH2-[O-(CH2)2]n-. In certain embodiments R12is bond. In certain embodiments R12is alkyl. In certain embodiments R12is a divalent residue of a natural amino acid. In certain embodiments R12is a divalent residue of an unnatural amino acid. In certain embodiments R13is bond. In certain embodiments R13is alkyl. In certain embodiments R13is C(O). In certain embodiments R13is -C(O)O-. In certain embodiments R13is -C(O)NR6-. In certain embodiments R13is -O-. In certain embodiments R13is -NR6-. In certain embodiments R13is a divalent residue of a natural amino acid. In certain embodiments R13is a divalent residue of an unnatural amino acid. In certain embodiments R13is -CH2CH2-[O-(CH2)2]n-O-. In certain embodiments R13is -CH2CH2-[O-(CH2)2]n-NR6-. In certain embodiments R13is -CH2CH2-[O-(CH2)2]n-. In certain embodiments R14is bond. In certain embodiments R14is alkyl. In certain embodiments R14is a divalent residue of a natural amino acid. In certain embodiments R14is a divalent residue of an unnatural amino acid. In certain embodiments R15is bond. In certain embodiments R15is alkyl. In certain embodiments R15is C(O). In certain embodiments R15is -C(O)O-. In certain embodiments R15is -C(O)NR6-. In certain embodiments R15is -O-. In certain embodiments R15is -NR6-. In certain embodiments R15is a divalent residue of a natural amino acid. In certain embodiments R15is a divalent residue of an unnatural amino acid. In certain embodiments R15is -CH2CH2-[O-(CH2)2]n-O-. In certain embodiments R15is -CH2CH2-[O-(CH2)2]n-NR6-. In certain embodiments R15is -CH2CH2-[O-(CH2)2]n-. In certain embodiments R16is bond. In certain embodiments R16is alkyl. In certain embodiments R16is a divalent residue of a natural amino acid. In certain embodiments R16is a divalent residue of an unnatural amino acid. In certain embodiments R17is bond. In certain embodiments R17is alkyl. In certain embodiments R17is C(O). In certain embodiments R17is -C(O)O-. In certain embodiments R17is -C(O)NR6-. In certain embodiments R17is -O-. In certain embodiments R17is -NR6-. In certain embodiments R17is a divalent residue of a natural amino acid. In certain embodiments R17is a divalent residue of an unnatural amino acid. In certain embodiments R17is -CH2CH2-[O-(CH2)2]n-O-. In certain embodiments R17is -CH2CH2-[O-(CH2)2]n-NR6-. In certain embodiments R17is -CH2CH2-[O-(CH2)2]n-. In certain embodiments R18is bond. In certain embodiments R18is alkyl. In certain embodiments R18is a divalent residue of a natural amino acid. In certain embodiments R18is a divalent residue of an unnatural amino acid. In certain embodiments R19is bond. In certain embodiments R19is alkyl. In certain embodiments R19is C(O). In certain embodiments R19is -C(O)O-. In certain embodiments R19is -C(O)NR6-. In certain embodiments R19is -O-. In certain embodiments R19is -NR6-. In certain embodiments R19is a divalent residue of a natural amino acid. In certain embodiments R19is a divalent residue of an unnatural amino acid. In certain embodiments R19is -CH2CH2-[O-(CH2)2]n-O-. In certain embodiments R19is -CH2CH2-[O-(CH2)2]n-NR6-. In certain embodiments R19is -CH2CH2-[O-(CH2)2]n-. In certain embodiments R20is bond. In certain embodiments R20is alkyl. In certain embodiments R20is a divalent residue of a natural amino acid. In certain embodiments R20is a divalent residue of an unnatural amino acid. In certain embodiments n is 0. In certain embodiments n is 1. In certain embodiments n is 2. In certain embodiments n is 3. In certain embodiments n is 4. In certain embodiments n is 5. In certain embodiments n is 6. In certain embodiments n is 7. In certain embodiments n is 8. In certain embodiments n is 9. In certain embodiments n is 10. Embodiments of R21In certain embodiments R21is hydrogen. In certain embodiments R21is alkyl. In certain embodiments R21is methyl. In certain embodiments R21is F. In certain embodiments R21is Cl. In certain embodiments R21is haloalkyl. In certain embodiments R21is C(O)R3. In certain embodiments R21is NH2. In certain embodiments R21is OH. Embodiments of R22In certain embodiments R22is alkyl. In certain embodiments R22is -C(O)N-. In certain embodiments R22is -NC(O)-. In certain embodiments R22is -N-. In certain embodiments R22is -C(R21)-. In certain embodiments R22is -P(O)O-. In certain embodiments R22is -P(O)-. In certain embodiments R22is -P(O)(NR6R7)N-. In certain embodiments R22is alkenyl. In certain embodiments R22is haloalkyl. In certain embodiments R22is aryl. In certain embodiments R22is heterocycle. In certain embodiments R22is heteroaryl. Embodiments of R32In certain embodiments R32is alkyl. In certain embodiments R32is N+X-. In certain embodiments R32is -C-. In certain embodiments R32is alkenyl. In certain embodiments R32is haloalkyl. In certain embodiments R32is aryl. In certain embodiments R32is heterocycle. In certain embodiments R32is heteroaryl. In certain embodiments X- is Br-. or; In certain embodiments X- is Cl-. Embodiments of R42In certain embodiments R42is hydrogen. In certain embodiments R42is alkyl. In certain embodiments R42is alkyl-O-alkyl. In certain embodiments R42is C(O)R43. In certain embodiments R42is C(O)Me. Embodiments of R43In certain embodiments R43is hydrogen. In certain embodiments R43is alkyl. In certain embodiments R43is haloalkyl. Embodiments of R65, R66, and R67In certain embodiments R65, R66, and R67are independently selected from hydrogen, halogen, and haloalkyl. In certain embodiments R65is hydrogen. In certain embodiments R65is alkyl. In certain embodiments R65is methyl. In certain embodiments R65is halogen. In certain embodiments R65is F. In certain embodiments R65is Cl. In certain embodiments R65is haloalkyl. In certain embodiments R65is CF3. In certain embodiments R65is OMe. In certain embodiments R65is OH. In certain embodiments R65is NH2. In certain embodiments R65is NHMe. In certain embodiments R65is NMe2. In certain embodiments R65is heterocycle. In certain embodiments R66is hydrogen. In certain embodiments R66is alkyl. In certain embodiments R66is methyl. In certain embodiments R66is halogen. In certain embodiments R66is F. In certain embodiments R66is Cl. In certain embodiments R66is haloalkyl. In certain embodiments R66is CF3. In certain embodiments R66is OMe. In certain embodiments R66is OH. In certain embodiments R66is NH2. In certain embodiments R66is NHMe. In certain embodiments R66is NMe2. In certain embodiments R66is heterocycle. In certain embodiments R67is hydrogen. In certain embodiments R67is alkyl. In certain embodiments R67is methyl. In certain embodiments R67is halogen. In certain embodiments R67is F. In certain embodiments R67is Cl. In certain embodiments R67is haloalkyl. In certain embodiments R67is CF3. In certain embodiments R67is OMe. In certain embodiments R67is OH. In certain embodiments R67is NH2. In certain embodiments R67is NHMe. In certain embodiments R67is NMe2. In certain embodiments R67is heterocycle. Embodiments of R75and R76In certain embodiments R75and R76are independently selected from hydrogen, halogen, and haloalkyl. In certain embodiments R75is hydrogen. In certain embodiments R75is alkyl. In certain embodiments R75is methyl. In certain embodiments R75is halogen. In certain embodiments R75is F. In certain embodiments R75is Cl. In certain embodiments R75is haloalkyl. In certain embodiments R75is CF3. In certain embodiments R75is OMe. In certain embodiments R75is OH. In certain embodiments R75is NH2. In certain embodiments R75is NHMe. In certain embodiments R75is NMe2. In certain embodiments R75is heterocycle. In certain embodiments R76is hydrogen. In certain embodiments R76is alkyl. In certain embodiments R76is methyl. In certain embodiments R76is halogen. In certain embodiments R76is F. In certain embodiments R76is Cl. In certain embodiments R76is haloalkyl. In certain embodiments R76is CF3. In certain embodiments R76is OMe. In certain embodiments R76is OH. In certain embodiments R76is NH2. In certain embodiments R76is NHMe. In certain embodiments R76is NMe2. In certain embodiments R76is heterocycle. Embodiments of R80In certain embodiments R80is hydrogen. In certain embodiments R80is alkyl. In certain embodiments R80is methyl. In certain embodiments R80is halogen. In certain embodiments R80is F. In certain embodiments R80is Cl. In certain embodiments R80is haloalkyl. In certain embodiments R80is CF3. In certain embodiments R80is OMe. In certain embodiments R80is OH. In certain embodiments R80is NH2. In certain embodiments R80is NHMe. In certain embodiments R80is NMe2. In certain embodiments R80is -C(O)R3. Embodiments of R102In certain embodiments R102is hydrogen. In certain embodiments R102is alkyl. In certain embodiments R102is methyl. In certain embodiments R102is halogen. In certain embodiments R102is F. In certain embodiments R102is Cl. In certain embodiments R102is haloalkyl. In certain embodiments R102is CF3. In certain embodiments R102is OMe. In certain embodiments R102is OH. In certain embodiments R102is NH2. In certain embodiments R102is NHMe. In certain embodiments R102is NMe2. In certain embodiments R102is -C(O)R3. Embodiments of n, m, and p In certain embodiments nn is 0. In certain embodiments nn is 1. In certain embodiments nn is 2. In certain embodiments nn is 3. In certain embodiments m is 0. In certain embodiments m is 1. In certain embodiments m is 2. In certain embodiments m is 3. In certain embodiments p is 0. In certain embodiments p is 1. In certain embodiments p is 2. In certain embodiments p is 3. Embodiments of ASGPR Binder B1. In certain embodiments a compound of Formula I, Formula II, or Formula III is provided wherein, the ASGPR Binding Ligand is selected from:

[0032] ; Q is -O- or -N(R10)-; R1and R5are independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-cyano, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, or C0-C6alkyl-O-S(O)2R3; in certain embodiments R1is hydrogen; R2is hydrogen, alkyl, or C(O)R3; R3at each occurrence is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, -OR8, and -NR8R9; R6and R7are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R8and R9are independently selected at each occurrence from hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocycle; R10is hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, C(O)R3, S(O)R3, C(S)R3, or S(O)2R3; in certain embodiments R10is hydrogen; R65, R66, and R67are independently selected at each occurrence from the group consisting of hydrogen, C0-C6alkyl-cyano, alkyl, alkenyl, alkynyl, haloalkyl, F, Cl, Br, I, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl- C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, and C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from R80; R80is independently selected at each instance from the group consisting of alkyl (including C1-C4alkyl), alkenyl (including C2-C4alkenyl), alkynyl (including C2-C4alkynyl), haloalkyl (including C1-C4haloalkyl), -OR6, F, Cl, Br, I, -NR6R7, heterocycle, heteroaryl, aryl, cyano, nitro, hydroxyl, azide, amide, -SR6, -S(O)(NR6)R3, -NR8C(O)R3, -C(O)NR6R7, and -C(O)R3; B2. The compound of embodiment B1, wherein the compound is selected from . B3. The compound of embodiment B1, wherein the compound is selected from

[0033] . 3, wherein R65is not substituted with an optional substituent. B5. The compound of any one of embodiments B1-B3, wherein R65is substituted with 1 optional substituent. B6. The compound of any one of embodiments B1-B3, wherein R65is substituted with 2 optional substituents. B7. The compound of any one of embodiments B1-B3, wherein R65is substituted with 3 optional substituents. B8. The compound of any one of embodiments B1-B3, wherein R65is hydrogen. B9. The compound of any one of embodiments B1-B3, wherein R65is -CF3. B10. The compound of any one of embodiments B1-B3, wherein R65is cyano. B11. The compound of any one of embodiments B1-B3, wherein R65is F. B12. The compound of any one of embodiments B1-B3, wherein R65is Cl. B13. The compound of any one of embodiments B1-B3, wherein R65is Br. B14. The compound of any one of embodiments B1-B7, wherein R65is haloalkyl. B15. The compound of any one of embodiments B1-B7, wherein R65is heterocycle. B16. The compound of any one of embodiments B1-B7, wherein R65is haloalkoxy. B17. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl-OR6. B18. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl-SR6. B19. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- NR6R7. B20. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- C(O)R3. B21. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- S(O)R3. B22. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- C(S)R3. B23. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- S(O)2R3. B24. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- N(R8)-C(O)R3. B25. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- N(R8)-S(O)R3. B26. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- N(R8)-C(S)R3. B27. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- N(R8)-S(O)2R3. B28. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkylN3. B29. The compound of any one of embodiments B1-B7, wherein R65is C0-C6alkyl- cyano. B30. The compound of any one of embodiments B17-B29, wherein C0-C6alkyl is C0- alkyl (i.e. bond). B31. The compound of any one of embodiments B17-B29, wherein C0-C6alkyl is C1- alkyl. B32. The compound of any one of embodiments B17-B29, wherein C0-C6alkyl is C2- alkyl. B33. The compound of any one of embodiments B1-B7, wherein R65is -N=S(O)(R3)2. B34. The compound of any one of embodiments B1-B7, wherein R65is heterocycloalkyl. B35. The compound of any one of embodiments B1-B7, wherein R65is aryl. B36. The compound of any one of embodiments B1-B35, wherein R66is not substituted with an optional substituent. B37. The compound of any one of embodiments B1-B35, wherein R66is substituted with 1 optional substituent. B38. The compound of any one of embodiments B1-B35, wherein R66is substituted with 2 optional substituents. B39. The compound of any one of embodiments B1-B35, wherein R66is substituted with 3 optional substituents. B40. The compound of any one of embodiments B1-B35, wherein R66is hydrogen. B41. The compound of any one of embodiments B1-B35, wherein R66is -CF3. B42. The compound of any one of embodiments B1-B35, wherein R66is cyano. B43. The compound of any one of embodiments B1-B35, wherein R66is F. B44. The compound of any one of embodiments B1-B35, wherein R66is Cl. B45. The compound of any one of embodiments B1-B35, wherein R66is Br. B46. The compound of any one of embodiments B1-B37, wherein R66is haloalkyl. B47. The compound of any one of embodiments B1-B37, wherein R66is heterocycle. B48. The compound of any one of embodiments B1-B37, wherein R66is haloalkoxy. B49. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- OR6. B50. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl-SR6. B51. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- NR6R7. B52. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- C(O)R3. B53. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- S(O)R3. B54. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- C(S)R3. B55. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- S(O)2R3. B56. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- N(R8)-C(O)R3. B57. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- N(R8)-S(O)R3. B58. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- N(R8)-C(S)R3. B59. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- N(R8)-S(O)2R3. B60. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkylN3. B61. The compound of any one of embodiments B1-B37, wherein R66is C0-C6alkyl- cyano. B62. The compound of any one of embodiments B49-B61, wherein C0-C6alkyl is C0- alkyl (i.e. bond). B63. The compound of any one of embodiments B49-B61, wherein C0-C6alkyl is C1- alkyl. B64. The compound of any one of embodiments B49-B61, wherein C0-C6alkyl is C2- alkyl. B65. The compound of any one of embodiments B1-B35, wherein R66is -N=S(O)(R3)2. B66. The compound of any one of embodiments B1-B35, wherein R66is heterocycloalkyl. B67. The compound of any one of embodiments B1-B35, wherein R66is aryl. B68. The compound of any one of embodiments B1-B67, wherein R67is not substituted with an optional substituent. B69. The compound of any one of embodiments B1-B67, wherein R67is substituted with 1 optional substituent. B70. The compound of any one of embodiments B1-B67, wherein R67is substituted with 2 optional substituents. B71. The compound of any one of embodiments B1-B67, wherein R67is substituted with 3 optional substituents. B72. The compound of any one of embodiments B1-B67, wherein R67is hydrogen. B73. The compound of any one of embodiments B1-B67, wherein R67is -CF3. B74. The compound of any one of embodiments B1-B67, wherein R67is cyano. B75. The compound of any one of embodiments B1-B67, wherein R67is F. B76. The compound of any one of embodiments B1-B67, wherein R67is Cl. B77. The compound of any one of embodiments B1-B67, wherein R67is Br. B78. The compound of any one of embodiments B1-B67, wherein R67is haloalkyl. B79. The compound of any one of embodiments B1-B65, wherein R67is heterocycle. B80. The compound of any one of embodiments B1-B67, wherein R67is haloalkoxy. B81. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- OR6. B82. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl-SR6. B83. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- NR6R7. B84. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- C(O)R3. B85. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- S(O)R3. B86. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- C(S)R3. B87. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- S(O)2R3. B88. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- N(R8)-C(O)R3. B89. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- N(R8)-S(O)R3. B90. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- N(R8)-C(S)R3. B91. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- N(R8)-S(O)2R3. B92. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkylN3. B93. The compound of any one of embodiments B1-B67, wherein R67is C0-C6alkyl- cyano. B94. The compound of any one of embodiments B81-B93, wherein C0-C6alkyl is C0- alkyl (i.e. bond). B95. The compound of any one of embodiments B81-B93, wherein C0-C6alkyl is C1- alkyl. B96. The compound of any one of embodiments B81-B93, wherein C0-C6alkyl is C2- alkyl. B97. The compound of any one of embodiments B1-B67, wherein R67is -N=S(O)(R3)2. B98. The compound of any one of embodiments B1-B67, wherein R67is heterocycloalkyl. B99. The compound of any one of embodiments B1-B67, wherein R67is aryl. B100. The compound of embodiment B3, wherein heteroar . B101. The compound of embodiment B3, wherein heteroary . B102. The compound of embodiment B3, wherein heteroaryl i . B103. The compound of embodiment B3, wherein heteroar . B104. The compound of embodiment B3, wherein heteroar . B105. The compound of embodiment B3, wherein heteroaryl i . B106. The compound of embodiment B3, wherein heteroaryl i . B107. The compound of embodiment B3, wherein heteroaryl . B108. The compound of embodiment B3, wherein heteroar . B109. The compound of embodiment B3, wherein heteroar . B110. The compound of embodiment B3, wherein heteroaryl i . B111. The compound of embodiment B3, wherein heteroaryl i . B112. The compound of embodiment B3, wherein heteroary . B113. The compound of embodiment B3, wherein heteroaryl . B114. The compound of embodiment B3, wherein heteroar . B115. The compound of embodiment B3, wherein heteroar . B116. The compound of embodiment B3, wherein heteroar . B117. The compound of embodiment B3, wherein heteroary . B118. The compound of embodiment B3, wherein heteroary . B119. The compound of embodiment B3, wherein heteroar . B120. The compound of embodiment B3, wherein heteroaryl i . B121. The compound of embodiment B3, wherein heteroaryl . B122. The compound of any one of embodiments B1-B121, hydrogen. B123. The compound of any one of embodiments B1-B121, wherein R10is alkyl. B124. The compound of any one of embodiments B1-B121, wherein R10is methyl. B125. The compound of any one of embodiments B1-B121, wherein R10is deuterium. B126. The compound of any one of embodiments B1-B121, wherein R10is C(O)R3. B127. The compound of any one of embodiments B1-B121, wherein R10is arylalkyl. B128. The compound of any one of embodiments B1-B127, wherein R1is hydrogen. B129. The compound of any one of embodiments B1-B127, wherein R1is hydrogen. B130. The compound of any one of embodiments B1-B127, wherein R1is aryl. B131. The compound of any one of embodiments B1-B127, wherein R1is phenyl. B132. The compound of any one of embodiments B1-B127, wherein R1is C(O)R3. B133. The compound of any one of embodiments B1-B127, wherein R1is arylalkyl. B134. The compound of any one of embodiments B1-B127, wherein R1is alkyl. B135. The compound of any one of embodiments B1-B127, wherein R1is haloalkyl. B136. The compound of any one of embodiments B1-B127, wherein R1is methyl. B137. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- cyano. B138. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- OR6B139. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl-SR6B140. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- NR6R7B141. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- C(O)R3B142. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- S(O)R3B143. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- S(O)2R3B144. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- N(R8)-C(O)R3B145. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- N(R8)-S(O)R3B146. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl- N(R8)-S(O)2R3B147. The compound of any one of embodiments B1-B127, wherein R1is C0-C6alkyl-O- C(O)R3B148. The compound of any one of embodiments B137-B147, wherein C0-C6alkyl is C0- alkyl (i.e. bond). B149. The compound of any one of embodiments B137-B147, wherein C0-C6alkyl is C1- alkyl. B150. The compound of any one of embodiments B137-B147, wherein C0-C6alkyl is C2- alkyl. In certain embodiments R65, R66, or R67is aryl. In certain embodiments R65, R66, or R67is heteroaryl. In certain embodiments R65, R66, or R67is heterocycle. V. METHODS OF TREATMENT In certain aspects, the apoB degrading compound of the current invention can be administered in an effective amount for the treatment of a medical disorder which can be treated by lowering apoB levels, for example high cholesterol or cardiovascular disease. In some embodiments, the apoB degrading compound of the current invention lowers apoB levels. In some embodiments, the apoB degrading compound of the current invention lowers apoB-100 levels. In certain aspects, the apoB degrading compound of the current invention degrades apoB which is incorporated into a lipoprotein particle. In some embodiments, the apoB degrading compound binding to apoB which is incorporated into a lipoprotein particle results in degradation of the lipoprotein particle. In some embodiments, the apoB degrading compound of the current invention degrades lipoprotein particles comprising apoB. In some embodiments, the apoB degrading compound of the current invention is used to decrease cholesterol levels, in particular LDL cholesterol levels. In some embodiments, the apoB degrading compound decreases the levels of atherogenic lipoproteins. In some embodiments, the apoB degrading compound decreases the levels of IDL. In some embodiments, the apoB degrading compound decreases the levels of LDL. In some embodiments, the apoB degrading compound decreases the levels of VLDL. In some embodiments, the apoB degrading compound of the current invention is used to treat a patient with cardiovascular disease or who is at risk of developing cardiovascular disease, including those with a family history or cardiovascular disease. In some embodiments, the apoB degrading compound of the current invention is used to treat a patient with familial hypercholesterolemia. In some embodiments, the apoB degrading compound of the current invention is used to treat a patient with familial combined hyperlipidemia. In some embodiments, a compound of the present invention is used to treat a patient with an LDLR mutation. In some embodiments, the LDLR mutation is a class I, class II, class III, class IV, class V, or class VI mutation. In some embodiments, the LDLR mutation encodes an amino acid substitution selected from C27W, C46S, A50S, S56P, R78C, W87G, C89Y, D90G, D90N, D90Y, Q92E, C95G, E101K, C116R, C134F, C134W, D139H, E140K, C143R, C148Y, C155Y, C160Y, D168H, D168N, D168Y, D172H, D172N, C173W, D175N, D175Y, S177L, C184W, C184Y, C197R, E201K, H211L, D221G, D221N, D221Y, C222Y, D224V, D227E, E228K, 32281, C231G, C243R, C248Y, Q254P, C255S, C261F, D266E, C276R, C276W, E277K, S286R, E288K, R300G, D301A, D301G, C302W, C302Y, D304N, S306L, C313Y, C318F, C318R, S326C, H327Y, C329F, C329Y, C338F, C338S, G343S, R350P, C352R, D356Y, C358Y, Q366R, C368R, C368Y, N370T, G373D, C379Y, D378P, C386Y, A399D, A399T, L401H, L401V, F403L, T404P, R406Q, E408K, T413M, L414R, D415G, R416Q, R416W, I423T, V429M, A431T, L432V, D433H, T434K, Y442H, I451T, T454N, V468I, R471G, L479P, D482H, W483R, D492N, V523M, P526S, P526T, G549D, N564H, N564S, R574C, R574H, W577G, W577R, W577S, D579N, D579Y, S584P, I585T, G592E, R595W, D601H, A606S, P608S, D622G, R633C, V639D, P649L, H656N, T659N, C667Y, P685L, C698Y, D700E, D700G, D707Y, E714K, T726I, T742I, V806D, R814Q, N825K, Y828C, G844D, or a combination thereof. As used herein, the phrase “control serum levels” refers to a level of a particular serum component in the absence of treatment according to the present invention. In some embodiments, the “control serum level” is a level of a particular serum component in the subject prior to treatment of the subject according to the present invention. In some embodiments, the “control serum level” is the level of a particular serum component in a subject receiving a placebo treatment. In some embodiments, the “control serum level” is the level of a particular serum component in a subject receiving a different treatment. Serum components, include, for example, cholesterol, triglycerides, and apolipoprotein B, and can be determined by comparing pre-treatment levels to levels during or after treatment according to the present invention. Methods of measuring levels of particular components of serum are well-known to those of skill in the art. For example, total plasma cholesterol and triglyceride concentrations may be determined by a modification of the Liebermann-Burchard reaction (Abell, L.L. et al. A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem.195:357-362(1952) and by the Kessler and Lederer method, (Kessler, G. & Lederer, H. Fluorometric measurement of triglycerides. In: Skeggs L T, Jr, eds. Automation in Analytical Chemistry: Technicom Symposia. New York, N.Y.: Madiad Inc.341-344(1965)). Plasma HDL cholesterol may be estimated by the Allain et al. method (Allain, C.C. et al. Enzymatic determination of total serum cholesterol. Clin Chem.20:470-475(1974)) using an enzymatic kit. LDL-C may be calculated using the Freidewald formula (Freidewald, W.T. et al. Estimation of the concentration of low density lipoprotein- cholesterol in plasma without the use of the preparative ultracentrifuge. Clin Chem. 18:499- 502(1972)). Plasma apoB, apoA1, and lipoprotein(a) levels may be measured by immunological assays (Guo, H. et al. Lipoprotein Lp(a) in homozygous familial hypercholesterolemia: density profile, particle heterogeneity and apolipoprotein(a) phenotype. Atherosclerosis.31:69-83)(1991)) and laser immunonephelometry (Immuno AG). In some embodiments, the apoB degrading compound of the current invention is used to decrease cholesterol levels in a patient with atherosclerosis, coronary artery disease, cerebrovascular disease, or peripheral artery disease. In some embodiments, the apoB degrading compound of the current invention is used to decrease atherogenic lipoproteins in a patient with atherosclerosis, coronary artery disease, cerebrovascular disease, or peripheral artery disease. In some embodiments, the apoB degrading compound of the current invention reduces LDL particle numbers in a patient in need thereof. In some embodiments, the apoB degrading compound of the current invention reduces one or more of total cholesterol levels, plasma LDL-C levels, TG levels, fasting TG levels, VLDL levels, lipoprotein(a) (Lp(a)) levels, or Apolipoproteins A-I, A-II, B, and E levels in the subject by at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, or more than about 80% compared to control serum levels. In some embodiments, the patient having having a medical disorder is refractory to one or more prior therapies. In some embodiments, the patient having a medical disorder is refractory to a previously administered first line (1L) therapy. In some embodiments, the patient having a medical disorder is refractory to a previously administered second line (2L) therapy. In some embodiments, the patient having a medical disorder is refractory to a previously administered third line (3L) therapy. In some embodiments, the medical disorder to be treated using an apoB degrading compound as described herein is selected from Renal Artery Stenosis, Atherosclerotic Cardiovascular Disease (ASCVD), Atherosclerosis, Aneurysm, Stroke, Transient Ischemic Attack, Coronary Heart Disease, Acute Coronary Syndrome, Myocardial Infarction, Angina Pectoris, Heart Failure, Coronary Artery Stenosis, Peripheral Vascular Disease, Post-Coronary Revascularization, ASCVD with Elevated Lipoprotein(a), Mixed Dyslipidemia, Hypercholesterolemia, Hyperlipidemia, Hypertriglyceridemia, Severe Hypertriglyceridemia, Familial Hypercholesterolemia (Type II Hyperlipoproteinemia) , Heterozygous Familial Hypercholesterolemia (HeFH) , Homozygous Familial Hypercholesterolemia (HoFH) , ASCVD Primary Prevention, ASCVD Primary Prevention with Elevated Lipoprotein(a), Familial Chylomicronemia Syndrome, Metabolic Syndrome, NAFLD, NASH, Complications of Type II Diabetes, or Complications of Chronic Kidney Disease. Hypercholesterolemia (HCL) In some embodiments, the medical disorder to be treated is Hypercholesterolemia (HCL). HCL is a condition that is characterized by high levels of blood lipoproteins and cholesterol and is associated with the risk of developing atherosclerotic cardiovascular disease (ASCVD). Lipoproteins comprise lipids and protein and are transported in plasma for the delivery of cholesterol, triglycerides (TGs), and fat-soluble vitamins to certain organs. High cholesterol levels in HCL are classified by LDL-C >190 mg / dL, alternatively >160 mg / dL with one major cardiovascular risk factor, or alternatively >130 mg / dL with two major cardiovascular risk factors. Major cardiovascular risk factors include 1) age (male >45-years old, female >55-years old); 2) family of premature atherosclerotic cardiovascular disease (male <55-years old; female <65-years old); 3) hypertension; 4) diabetes; 5) smoking; and 6) low HDL-C levels (male <40 mg / dl; female <55 mg / dl). According to the CDC, approximately 31.7% of adults in the United States have elevated levels of LDL-C. While this estimated population of 73.5 million patients have double the risk for heart disease than adults with normal levels of LDL-C, only about 48.1% of these receive treatment to lower LDL-C levels. In some embodiments, the apoB degrading compound of the current invention is used to treat a human having HCL to prevent the development of ASCVD. Cases of HCL can either be acquired or inherited. In some embodiments, the apoB degrading compound of the current invention is used to treat a human having acquired HCL. In some embodiments, the apoB degrading compound of the current invention is used to treat a human having familial HCL. Familial Hypercholesterolemia (Type II Hyperlipoproteinemia) In some embodiments, the medical disorder to be treated is Familial Hypercholesterolemia (Type II Hyperlipoproteinemia). Familial hypercholesterolemia (FH) is an inherited disease characterized by abnormally increased levels of LDL-C in serum that affects ~1 in every 220 individuals globally (Sturm, A.C. et al. Convened by the Familial Hypercholesterolemia Foundation. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 72:662– 680(2018)). Elevated LDL-C is a life-long condition that eventually leads to the development of cardiovascular disease (CVD). Most commonly, cases of FH are caused by autosomal dominant low-density lipoprotein receptor (LDLR) mutations. Other cases of FH are caused by mutations in genes encoding for proteins involved in cholesterol metabolism and / or LDLR formation / function. Mutations in these genes, for example apolipoprotein B (APOB) or proprotein convertase subtilisin / kexin 9 (PCSK9), can lead to familial hypercholesterolaemia as well but are less common. Pathogenic APOB mutants (most commonly mutation of position 3500) result in increased binding of LDL to LDLR and comprise 5%-15% of FH cases (Soutar, A.K. & Naoumova, R.P. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med.4:214–225(2007)). Gain-of-function mutations in PCSK9 comprise about 1% of FH cases (See Id.), in which LDLR is more rapidly cleared and targeted to the lysosome for degradation in the liver. More than 1600 total mutations have been associated with FH. In some embodiments, the patient with Familial Hypercholesterolemia harbors a mutation in LDLR. In some embodiments, the patient with Familial Hypercholesterolemia is statin resistant or intolerant. In some embodiments, the familial hypercholesterolemia is selected from heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH). Heterozygous Familial Hypercholesterolemia (HeFH) In some embodiments, the medical disorder to be treated is Heterozygous Familial Hypercholesterolemia (HeFH). HeFH affects approximately 1 in every 250 individuals and is associated with an increased risk of early coronary artery disease (CAD). HeFH is commonly associated with elevated plasma LDL-C levels (> 190 mg / dl) and xanthomas (i.e., cholesterol deposits) affecting the corneas, eyelids, and extensor tendons. HeFH is also associated with accelerated vascular disease, especially coronary artery disease (CAD). Individuals who are heterozygous for FH have a 50% chance of passing FH to their children. HeFH is typically treated with combination drug therapy to lower serum LDL-C. Homozygous Familial Hypercholesterolemia (HoFH) In some embodiments, the medical disorder to be treated is Homozygous Familial Hypercholesterolemia (HoFH). Homozygous familial hypercholesterolemia (HoFH) is a potentially lethal disease caused by homozygosity or compound heterozygosity for mutations in LDLR or other genes. HoFH affects approximately 1 in every 300,000 individuals. HoFH is characterized by elevated total plasma cholesterol levels (> 450 mg / dl) and premature development of atherosclerotic vascular disease. HoFH is a rare (affecting less than one individual per million) but critical condition in which pathognomonic symptoms can be observed in the first years of childhood, including xanthelasmas, tendon xanthomas, and corneal arcus. It is principally noted in countries such as Lebanon, Canada, and South Africa possibly because of the founder mutations and isolation of population (Marais AD. Familial hypercholesterolaemia. Clin Biochem Rev.2004;25:49–68). If left untreated, most individuals with HoFH develop atherosclerosis by 20 and do not live past the age of 30. Patients having HoFH are poorly responsive to conventional drug therapy and have limited treatment options. For example, use of statins fail to sufficiently reduce LDL-C because patients with HoFH have LDL receptors that are either non-existent or defective. For example, patients with genotype- confirmed HoFH treated with maximum doses of statins (atorvastatin or simvastatin 80 mg / day) demonstrated only about 5.5% reduction of LDL-C. Addition of ezetimibe at 10 mg / day resulted in only about 27% LDL-C reduction. The primary goal of therapy therefore is to control hypercholesterolemia to delay the development of atherosclerotic cardiovascular disease (ASCVD). The current standard of care in HoFH remains LDL apheresis, a method of filtering the plasma selectively remove apoB-containing lipoproteins using affinity columns, which can transiently reduce LDL-C by about 50%. LDL apheresis must be repeated weekly or biweekly and requires 2 separate sites for IV access. Compliance of an LDL apheresis is expensive and difficult to maintain, and therefore, there is a tremendous unmet medical need for new therapies for hoFH. ASCVD Primary Prevention In some embodiments, the medical disorder to be treated is ASCVD Primary Prevention. ASCVD Primary Prevention refers to efforts to treat Hypercholesterolemia (HCL) patients at risk of developing ASCVD. In some embodiments, the patients to be treated is an intermediate risk patient having between about 7.5% and about 20% of a 10-year risk of a cardiovascular event. In some embodiments, the patients to be treated is an intermediate risk patient having about or greater than about 20% of a 10-year risk of a cardiovascular event. ASCVD Primary Prevention with Elevated Lipoprotein(a) In some embodiments, the medical disorder to be treated is ASCVD Primary Prevention with Elevated Lipoprotein(a) (Lp(a)). In some embodiments, elevated Lp(a) comprises greater than about 50 mg / dl serum Lp(a). In some embodiments, elevated Lp(a) comprises between about 31 to about 50 mg / dl serum Lp(a). In some embodiments, elevated Lp(a) comprises between about 14 to about 30 mg / dl serum Lp(a). Atherosclerosis In some embodiments, the medical disorder to be treated is Atherosclerosis. Atherosclerosis is a chronic, slowly progressing disease characterized by accumulation of lipids (plaques) which induce inflammation of large arteries. Atherosclerosis is the major cause of cardiovascular disease (CVD) and stroke and is the leading cause of death (approximately 50% of all) worldwide. Atherosclerosis is mainly due to accumulation of LDL and remnant lipoprotein particles and focal areas of inflammation in arteries that disturb non-laminar flow at artery branch points. Turbulent flow in arteries caused by inflammation cause atherosclerotic cardiovascular disease (ASCVD) and results in myocardial infarctions (i.e., heart attacks), stroke, and peripheral artery disease. As a predominantly asymptomatic disease of slow progression, atherosclerosis occurs primarily in older individuals (male >45-years old, female>55-years old). The most common risk factors include sedentary lifestyle, obesity, poor diet, hypercholesterolemia, hypertension, diabetes, smoking, gender (male), and family history. Treatment of atherosclerosis includes but is not limited to cholesterol synthesis inhibitors (e.g., statins), beta-blockers, ACE inhibitors, angiotensin II receptor blockers (ARBs), diuretics, calcium channel blockers, and vasodilators. Atherosclerotic Cardiovascular Disease (ASCVD) In some embodiments, the medical disorder to be treated is Atherosclerotic Cardiovascular Disease (ASCVD). In some embodiments, the ASCVD comprises a medical disorder selected from Acute Coronary Syndrome (ACS), Myocardial Infarction (MI), ischemic stroke, or peripheral arterial disease (PAD). ASCVD is a leading cause of mortality, with over 380,000 deaths attributed to Cardiovascular Heart Disease (CHD) and over 160,000 deaths attributed to Stroke in the United States in 2020 (Tsao, C.W. et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation.147(8):e93- e621(2023 Feb 21)). Atherosclerosis involves chronic arterial wall lesion development due to lipid retention which evolve into fibrous plaques and eventually result in atherosclerotic lesions that risk rupture of the vessel. ApoB-containing lipoproteins, including LDL, Lp(a), and triglyceride (TG)-rich lipoproteins (TRLs), established risk factors for ASCVD, become trapped by proteoglycans on the arterial wall. Specifically, Lp(a) and TRLs are risk factors in comorbid conditions, for example, TRLs in diabetes and / or obesity. These risk factors are not well addressed by drugs that upregulate LDLR, including statins and PCSK9 inhibitor therapies. Low-Density Lipoprotein Cholesterol (LDL-C) Low-Density Lipoprotein Cholesterol (LDL-C), which is a measurement of cholesterol carried in LDL particles, is a cornerstone marker for cardiovascular risk. (Lawler, P.R. et al. Discordance between Circulating Atherogenic Cholesterol Mass and Lipoprotein Particle Concentration in Relation to Future Coronary Events in Women. Clin Chem.63(4):870-879(2017 Apr); Cantey, E.P. & Wilkins, J.T. Discordance between lipoprotein particle number and cholesterol content: an update. Curr Opin Endocrinol Diabetes Obes. 25(2):130-136(2018 Apr); Sniderman, A.D. et al. Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review. JAMA Cardiol.4(12):1287-1295(2019 Dec 1); Johannesen, C.D.L. et al. Apolipoprotein B and Non-HDL Cholesterol Better Reflect Residual Risk Than LDL Cholesterol in Statin-Treated Patients. J Am Coll Cardiol.77(11):1439-1450(2021 Mar 23); Marston, N.A. et al. Cardiovascular Benefit of Lowering Low-Density Lipoprotein Cholesterol Below 40 mg / dL. Circulation. 144(21):1732-1734(2021 Nov 23)). LDL-C is standard measure of cholesterol in LDL. In a meta- analysis of 26 statin trials, a 22% decrease in major vascular events per 39 mg / dl decrease in LDL- C was observed (CTT Collaboration, Baigent 2010, major vascular event defined as first occurrence of any major coronary event, coronary revascularisation, or stroke). There is evidence that apoB levels better correlate with ASCVD risk than LDL-C, but LDL-C is still targeted as the top treatment target in ASCVD (Cole, J. et al. A Translational Tool to Facilitate Use of Apolipoprotein B for Clinical Decision-Making. Clin Chem. 69(1):41-47(2023 Jan 4)). An estimated 634,000 ASCVD events, including 244,000 deaths, may be averted in the next 10 years if all ASCVD patients reduce LDL-C levels below the 70mg / dl target (McKinley 2023, events include Coronary Heart Disease, ischemic stroke, CV death). In support of this, long-term data from inhibition of PCSK9 demonstrate a further benefit that is achieved when LDL-C is reduced below the 70 mg / dl target (Gaba 2023 FOURIER-OLE). Although the current 70 mg / dl target provides numerous health benefits to individuals having ASCVD, the target remains “minimally acceptable”. All patients ideally should receive additional treatments to reduce LDL-C levels below 55 mg / dl as required by the new 2022 guidelines for very high risk ASCVD (Lloyd-Jones, D. et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. J Am Coll Cardiol.80(14):1366–1418(2022 Oct)). Apolipoprotein B (apoB) Apolipoprotien B (apoB) is believed to be a better predictor of ASCVD as it is found on additional atherogenic particles besides LDL. Measurements of LDL-C could actually underestimate cardiovascular disorder(s) risk as LDL-C do not include other atherogenic particles such as Lp(a) and triglyceride-rich VLDL. In many ways LDL particle number is a more important metric than LDL-C content. LDL-C is a measure of the cholesterol mass carried in LDL particles, whereas apoB more faithfully represent LDL particle number, and thus is a better predictor. Although LDL particle size is variable due to variable cholesterol masses, each particle is equally atherogenic regardless of size. For example, bigger LDL particles may deposit more cholesterol, but smaller LDL particles may be more easily trapped in an arterial wall. Triglyceride (TG) In some embodiments, triglyceride (TG) levels are lowered through VLDL degradation using an apoB degrading compound of the current invention. Elevated triglyceride levels associated with increased ASCVD risk. Mendelian randomization studies have found elevated TG levels are associated with ASCVD risk (Do, R. et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet. 45(11):1345-1352(2013 Nov)). Additional Mendelian randomization studies have found that, upon controlling for elevated non- HDL-C, the association of TGs with ASCVD tends toward zero. This suggests that elevated TG risk is acting through increased apoB particles (Holmes, M.V. et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J. 36(9):539-550(2015 Mar 1; Epub 2014 Jan 27). TG-rich lipoprotein particles (TRLs) can contribute to ASCVD through multiple mechanisms. TRLs are atherogenic particles – elevated TRLs increase the amount of apoB particles which drives an increased risk of ASCVD. Elevated TRLs are associated with a decrease in the size of LDL particles and this leads to a discrepancy between LDL-C and apoB measurement, thereby underestimating the risk at a given LDL-C level. Additionally, LDLR has reduced affinity for small LDL particles, which may lead to reduced apoB particle clearance in patients with elevated TGs. VLDL particles carry large amounts of TGs, which are additional risk factors for ASCVD. Current LDL-C lowering agents often have little or no impact on elevated TG levels. Strategies to lower VLDL may help additional cardiovascular disease risk in diabetic patients, who have high TG and an elevated lifetime risk of ASCVD. In some embodiments, the apoB degrading compound of the current invention reduces LDL particle numbers in a patient having ASCVD. In some embodiments, the apoB degrading compound of the current invention reduces one or more of total cholesterol levels, plasma LDL- cholesterol levels, triglyceride levels, fasting triglycerides (TG) levels, VLDL levels, lipoprotein(a) (Lp(a)) levels, or Apolipoproteins A-I, A-II, B, and E levels in the subject by at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, or more than about 80% compared to control serum levels. In some embodiments, the patient having ASCVD is refractory to one or more prior therapies. In some embodiments, the patient having ASCVD is refractory to a previously administered first line (1L) therapy. In some embodiments, the patient having ASCVD is refractory to a previously administered second line (2L) therapy. In some embodiments, the patient having ASCVD is refractory to a previously administered third line (3L) therapy. ASCVD with Elevated Lipoprotein(a) In some embodiments, the medical disorder to be treated is ASCVD with Elevated Lipoprotein(a). Lipoprotein(a) (Lp(a)) Lipoprotein(a) (Lp(a)), an orthogonal ASCVD risk factor, is a subtype of LDL with apolipoprotein(a) that is covalently bound to apoB100. Approximately 10-20% of the population have elevated Lp(a) levels greater than or equal to 70 mg / dL. Individuals having Lp(a) levels greater than 100 mg / dL (250 nmol / L) carry an ASCVD risk that is doubled, regardless of the individual’s baseline risk. Lp(a) concentration is primarily driven by genetic risk factors, for example the number of kringle repeats in apo(a). Importantly, most current LDL-lowering agents have low or negligible impact on Lp(a). Certain novel Lp(a)-lowering agents have achieved enhanced Lp(a) reduction. For example, the Amgen / Novartis siRNA olpasiran, which is currently in Phase 3 development, has achieved 80-98% reduction of Lp(a) in Phase 2 (O'Donoghue, M.L. et al. OCEAN(a)-DOSE Trial Investigators. Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease. N Engl J Med.387(20):1855-1864(2022 Nov 17)). Separately, the oral Lp(a) inhibitor muvalaplin achieved 65% max reduction in a Phase 1 trial (Swerdlow, D.I. et al. Treatment and prevention of lipoprotein(a)-mediated cardiovascular disease: the emerging potential of RNA interference therapeutics. Cardiovasc Res.118(5):1218-1231(2022 Mar 25)). In some embodiments, the ASCVD with Elevated Lp(a) comprises a serum Lp(a) level of greater than or equal to about 70 mg / dL. In some embodiments, the ASCVD with Elevated Lp(a) comprises a serum Lp(a) level of greater than or equal to about 100 mg / dL. Acute Coronary Syndrome In some embodiments, the medical disorder to be treated is Acute Coronary Syndrome (ACS). ACS is a type of coronary heart disease (CHD) that includes a group of conditions including ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina. ACS typically results from plaque occlusion in coronary arteries (i.e., atherosclerosis). Common risk factors of ACS are smoking, hypertension, diabetes, hyperlipidemia, gender (male), physical inactivity, obesity, and poor nutrition. Family history of early myocardial infarction (MI) is also a recognized important risk factor. Common symptoms of ACS include chest pain which radiates to jaw and / or arm and can also include difficulty breathing, lightheadedness, nausea, diaphoresis, and weakness. The major cause of death in individuals with ACS is a complication known as major adverse cardiac event (MACE), which comprises conditions selected from stroke, myocardial infarction (MI), cardiovascular death, or a combination thereof. Although apoB levels offer an added predictive metric beyond LDL-C to predict MACE in individuals with coronary heart disease (Kastelein, J.J. et al. Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation. 2008; 117:3002–3009; Sniderman, A.D. Differential response of cholesterol and particle measures of atherogenic lipoproteins to LDL-lowering therapy: implications for clinical practice. J Clin Lipidol.2008; 2:36–42) a similar predictive factor is not firmly established in individuals with ACS (Ray, K.K. et al. Prognostic utility of apoB / AI, total cholesterol / HDL, non-HDL cholesterol, or hs-CRP as predictors of clinical risk in patients receiving statin therapy after acute coronary syndromes: results from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol.2009; 29:424–430; Meeusen, J.W. et al. Lipid biomarkers for risk assessment in acute coronary syndromes.Curr Cardiol Rep.2017; 19:48). The relationship between apoB levels and MACE in ACS is critical, however, because Lp(a) and TRLs influence risk after ACS (Miller, M. et al. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol.2008; 51:724– 730; Schwartz, G.G. et al. Fasting triglycerides predict recurrent ischemic events in patients with acute coronary syndrome treated with statins. J Am Coll Cardiol. 2015; 65:2267–2275; Bittner, V.A. et al. Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome. J Am Coll Cardiol.2020; 75:133–144; O’Donoghue, M.L. et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation.2019; 139:1483–1492). Treatment of ACS generally includes but is not limited to aspirin, beta-blockers, ACE inhibitors, heparin, antiplatelet therapy. The prevention of cardiovascular events in individuals with ACS is managed by cholesterol synthesis inhibitors (e.g., statins), PCSK9 inhibitors, and cholesterol absorption inhibitors (e.g., ezetimibe) (Schwartz, G.G. et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA.2001; 285:1711–1718; Cannon, C.P. et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004; 350:1495–1504; Cannon CP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med.2015; 372:2387–2397; Sabatine, M.S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017; 376:1713–1722; Schwartz, G.G. et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018; 379:2097–2107). Statins and ezetimibe effectively lower serum levels of LDL-C while statins additionally lower TG-rich lipoproteins (TRLs), and PCSK9 inhibitors more effectively lower apoB-containing lipoproteins including Lp(a). Aneurysm In some embodiments, the medical disorder to be treated is Aneurysm. An Aneurysm is an abnormal enlargement of a blood vessel due to structural weakness of the vessel wall (Salameh, M.J. et al. Thoracic aortic aneurysm. Vasc Med. 23(6):573-578(2018 Dec)). A true Aneurysm commonly affect arteries and involves all three layers of the arterial wall (intima, media, and adventitia), whereas a false Aneurysm affects only the outer adventitia layer. Aneurysms may be cerebral and aortic, and either saccular or fusiform in shape. Aortic aneurysms are overwhelmingly fusiform (94%). Abdominal aortic aneurysms occur with failure of structural proteins of the aorta. Rupture of an aneurysm is a life-threatening condition. Risk factors for aneurysm primary comprises atherosclerosis but also include and are not limited to smoking, age, gender (male), race, family history of aneurysm, hypertension, hypercholesterolemia, and a prior history of aortic dissection. The therapeutic interventions for the treatment of aneurysm include but is not limited to blood pressure control (<130 / 80 mmHg) using, for example, beta-blockers, and cholesterol synthesis inhibitors (e.g., statins) (Salata, K. et al. Statins Reduce Abdominal Aortic Aneurysm Growth, Rupture, and Perioperative Mortality: A Systematic Review and Meta-Analysis. J Am Heart Assoc.7(19):e008657(2018 Oct 2)). Angina Pectoris In some embodiments, the medical disorder to be treated is Angina Pectoris. Chronic Angina Pectoris affects over 10 million adults in the United States and is the most common symptom of ischemic heart disease. Prevalence of Angina Pectoris increases with age in both men and women. Angina, or chest pain, is characterized by myocardial ischemia, which occurs when myocardial oxygen supply is insufficient. Angina Pectoris (Stable angina) is defined as the occurrence of symptoms with exertion only. This is in contrast to unstable angina in which symptoms occur at rest and which requires more immediate evaluation and management. An individual with stable angina has an average annual risk of 3%-4% for myocardial infarction or death. Angina is also a major sign of acute coronary syndrome (ACS). Chest pain in Angina Pectoris is caused by a mismatch of the increased demand of myocardial oxygen despite decreased supply of oxygen due to atherosclerosis of coronary arteries and coronary vasospasm during exertion. Increased oxygen demand during exertion is due to increased heart rate, increased blood pressure, increased myocardial contractility (Ferrari, R. et al. Expert consensus document: A 'diamond' approach to personalized treatment of angina. Nat Rev Cardiol.15(2):120-132(2018 Feb)). Risk factors for Angina Pectoris include but are not limited to hyperlipidemia, hypertension, tobacco use, diabetes, obesity, and Metabolic Syndrome. Treatment of Angina Pectoris is focused on managing symptoms and preventing the progression of serious cardiac events. In addition to lifestyle modifications, therapies for Angina Pectoris include but are not limited to beta-blockers, cholesterol synthesis inhibitors, aspirin, ACE inhibitors, angiotensin receptor blockers, ivabradine, non-dihydropyridine calcium channel blockers, dihydropyridine calcium channel blockers, nitrates, nicorandil, and ranolazine (Wee Y, Burns K, Bett N. Medical management of chronic stable angina. Aust Prescr.38(4):131-136(2015 Aug)). Complications of Chronic Kidney Disease In some embodiments, the medical disorder to be treated is Complications of Chronic Kidney Disease. Chronic kidney disease (CKD) is a condition of progressively deteriorating kidney health that is distinguished by complications including high blood pressure, anemia, hyperkalemia, metabolic acidosis, bone disorders, mineral disorders, hyperphosphatemia, hyperparathyroidism, hypertension, and nerve damage. CKD affects between about 8%-16% of individuals worldwide and is often poorly diagnosed. CDK is characterized by a glomerular filtration rate (GFR) of <60 mL / min / 1.73 m2, albuminuria of ≥30 mg per 24 hours, or kidney damage, for example hematuria or polycystic or dysplastic kidneys persisting for >3-months. CKD is primarily attributed to diabetes and hypertension, but glomerulonephritis, infection, environmental exposures, and genetic risk factors may also contribute to CKD risk. Complications of Type II Diabetes In some embodiments, the medical disorder to be treated is Complications of Type II Diabetes. Type 2 diabetes is a chronic metabolic disorder which is rapidly increasing in prevalence worldwide. Type 2 diabetes is primarily caused by lifestyle factors (e.g., sedentary lifestyle, smoking, alcohol use) and genetics. Approximately 55% of cases of Type 2 diabetes are linked to obesity. Complications of diabetes include but are not limited to cardiovascular disease (CVD), coronary artery disease (CAD), peripheral artery disease (PAD), cerebrovascular disease, blindness, kidney failure, amputation, hypoglycemia, diabetic ketoacidosis, hyperglycemic hyperosmolar state, hyperglycaemic diabetic coma, nephropathy, neuropathy, and retinopathy. Treatments for individuals with Type 2 diabetes include but are not limited to lifestyle modifications, obesity treatments, oral hypoglycemic agents, insulin sensitizers (e.g., metformin), cholesterol synthesis inhibtors (e.g., statins), PCSK9 inhibitors, Cholesterol absorption inhibitors (e.g., ezetimibe), ACE inhibitors, angiotensin receptor blocker (ARB) therapy, non-sulfonylurea secretagogues, thiazolidinediones, alpha glucosidase inhibitors, insulin, glucagon-like peptide 1 analogoues, dipeptidyl peptidase-IV inhibitors, sodium-glucose cotransporter 2 inhibitors, 11ß- hydroxysteroid dehydrogenase 1 inhibitors, insulin-releasing glucokinase activators, pancreatic- G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, metabolic inhibitors of hepatic glucose output, and quick-release bromocriptine. Coronary Artery Stenosis (CAS) In some embodiments, the medical disorder to be treated is Coronary Artery Stenosis (CAS). CAS is an atherosclerotic, degenerative disease defined by narrowing of the carotid artery. Atherosclerosis of the carotid artery is due to build-up of cholesterol-rich plaques which cause the artery to narrow over time and block blood flow. Risk factors for CAS include but are not limited to age, tobacco use, hypertension, and diabetes. Ischemia may occur in the carotid artery and results in transient ischemic attack (TIA) or stroke. Treatment of CAS includes but is not limited to antiplatelet therapy, cholesterol synthesis inhibitors (e.g., statins), and hypertension therapy. Coronary Heart Disease In some embodiments, the medical disorder to be treated is Coronary Heart Disease. Coronary Heart Disease is an umbrella condition for a variety of coronary medical disorders affecting the structure and overall health of the heart organ. About 366,000 Americans die from Coronary Heart Disease every year. Coronary Heart Disease is caused by atherosclerosis, which is occlusion of blood vessels and arteries due to cholesterol-rich plaque build-up on the vessel / arterial wall and creates a supply-demand mismatch of oxygen. Coronary Heart Disease can cause myocardial infarctions (i.e., heart attacks), stroke, heart failure, and peripheral artery disease (PAD). Approximately 18.2 million individuals in the United States have Coronary Artery Disease, the major form of coronary heart disease in the United States according to the CDC. Coronary Artery Disease represents over 2% of all diseases worldwide and 32.7% of all cardiovascular diseases. Treatment of Coronary Heart Disease includes but is not limited to cholesterol synthesis inhibitors (e.g., statins), aspirin, beta-blockers, ACE inhibitors, calcium channel blockers, nitrates, ranolazine, and P2Y12 inhibitors. In some embodiments, Coronary Heart Disease comprises Coronary Artery Disease. In some embodiments, Coronary Artery Disease is selected from Stable Ischemic Heart Disease (SIHD) and Acute Coronary Syndrome (ACS). Familial Chylomicronemia Syndrome In some embodiments, the medical disorder to be treated is Familial Chylomicronemia Syndrome. Familial hyperchylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations in lipoprotein lipase (LPL). FCS is associated with increased plasma levels of triglycerides (TGs) and chylomicrons (Falko, J.M. Familial Chylomicronemia Syndrome: A Clinical Guide For Endocrinologists. Endocr Pract. 24(8):756-763(2018 Aug)). Elevated triglyceride levels cause a variety of symptoms, for example acute pancreatitis (Tripathi, M. et al. THE PREVALENCE OF PROBABLE FAMILIAL CHYLOMICRONEMIA SYNDROME IN A SOUTHERN CALIFORNIA POPULATION. Endocr Pract. 27(1):71-76(2021 Jan)). FCS is underreported, however, although an estimated 3,000-5,000 individuals are believed to be affected. The majority of FCS (~80%) results from homozygous mutations in the lipoprotein lipase (LPL) gene. The remainder of cases (~20%) are caused by mutations in genes that lead to dysfunctional lipoprotein lipase enzyme including apolipoprotein C-II (APOC2), apolipoprotein A-V (APOA5), high-density lipoprotein binding protein 1 (GP1HBP1), and lipase maturation factor 1 (LMF1). Diagnosis of FCS includes blood TG levels >880 mg / dl in consecutive blood draws. FCS can be differentiated from hyperlipidemia with FCS patients having <100 mg / dl apoB II. Dietary modification is the main treatment avenue for FCS that is supplemented by therapies including but not limited to beta-blockers, thiazide diuretics, and exogenous estrogen. Heart Failure In some embodiments, the medical disorder to be treated is Heart Failure. Heart Failure is a medical disorder characterized by a failure of the heart to pump enough blood to service the body and can result from any disorder which impairs ventricular inflow or blood outflow to systemic circulation. An estimated 26 million people worldwide experience heart failure, which contributes to high healthcare costs and increased morbidity and mortality rates. Common symptoms include fatigue, dyspnea, and pulmonary and peripheral edema. Effective diagnosis and treatment helps to prevent recurrence and enhances patient outcomes. Heart failure remains the primary cause of hospitalization of the elderly and is the cause of about 8.5% of all cardiovascular-related deaths in the United States (Benjamin, E.J. et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 135(10):e146-e603(2017 Mar 07)). Incidence of Heart Failure increases with age with metabolic deficiency and sedentary lifestyle being major risk factors. After the age of 65, each 10-year age increase doubles men’s risk of heart failure whereas women’s risk of heart failure triples every 10- years (See Id.). Heart failure is classified based upon the subject’s symptoms and calculated left ventricular ejection fraction (LVEF). Heart failure as a result of left ventricular dysfunction is separated into separate categories including reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and heart failure with mid-range ejection fraction (HFmrEF). HFmrEF may be caused by a mix of left ventricular dysfunctions (i.e., systolic and diastolic heart failure). HFrEF is generally defined as an ejection fraction (EF) of <40%. HFpEF is generally defined as heart failure with an EF of >50%, whereas HFmrEF is defined as heart failure with an EF of between 40%-50%. Congestive heart failure, for example, is caused by one or more structural and / or functional abnormalities of the heart. While the majority of heart failure cases have been associated with coronary artery disease and myocardial infarction (MI) historically, recently diabetes has become one of the predominant predisposing factors for heart failure. Structural abnormalities include but are not limited to hypertension, valvular heart disease, myocarditis, congenital heart disease, or uncontrolled arrhythmia. Hyperlipidemia In some embodiments, the medical disorder to be treated is Hyperlipidemia. Hyperlipidemia is the primary metabolic disease in the developed world and is associated with several other conditions, including obesity, diabetes, renal failure, nephrotic syndrome, alcohol abuse, cirrhosis of the liver, and hypothyroidism. Hyperlipidemia is diagnosed in over 3 million adults in the United States and Europe and prevalence continues to increase. Hyperlipidemia is commonly identified by elevated levels (>90thpercentile) of one or more serum markers including total cholesterol, LDL-C, apoB, and TGs when compared to the general population. Hyperlipidemia is also distinguished by HDL levels in bottom 10thpercentile when compared to the general population (Fredrickson, D.S. An international classification of hyperlipidemias and hyperlipoproteinemias. Ann Intern Med. 75(3):471-472(1971 Sep)). It is estimated that almost half of all adults in the United States have elevated LDL levels, with under 35% of these individual properly treating this serious medical disorder with LDL medications. Elevated levels of LDL-C have been consistently demonstrated to increase an individual’s risk for atherosclerosis and subsequent heart disease. Managing hyperlipidemia to avoid subsequent, more life-threatening conditions such as ASCVD is known as “primary prevention”. Hyperlipidemia can be broadly defined into primary (familial) and secondary (acquired) hyperlipidemia. Acquired hyperlipidemia may be caused by a variety of risk factors including hypercholesterolemia (elevated LDL), poor diet, medications (e.g., amiodarone, glucocorticoids), hypothyroidism, diabetes, obesity, and / or poor lifestyle (Ballantyne, C.M.et al. Hyperlipidemia: diagnostic and therapeutic perspectives. J Clin Endocrinol Metab.85(6):2089-2112(2000 Jun)). Treatment of Hyperlipidemia includes but is not limited to cholesterol synthesis inhibitors (e.g., statins), cholesterol absorption inhibitors (e.g., ezetimibe), PCSK9 inhibitors (e.g., evolocumab). Hypertriglyceridemia In some embodiments, the medical disorder to be treated is Hypertriglyceridemia. Hypertriglyceridemia (HTG), an increasingly prevalent medical disorder, is a medical disorder characterized by aberrantly increased serum levels of triglycerides (TGs) and is associated with an increased risk of cardiovascular disease (CVD) and pancreatitis. The risk of pancreatitis correlates with TG level and markedly increases with >500 mg / dL TG. Pancreatitis can generally be prevented by reducing TG levels below 250 mg / dL to 500 mg / dL. While serum TGs are usually higher in men than in women, TG levels increase with age in both genders. HTG is caused by a number of factors including but not limited to genetic factors, impaired TG-rich lipoproteins clearance, and increased TG production. HTG can also be caused by certain medical conditions, including obesity, metabolic syndrome, Type 2 diabetes, hypothyroidism, Cushing's syndrome, chronic kidney disease, HIV, pregnancy, and certain autoimmune conditions such as systemic lupus erythematosus have been associated with HTG. Medications can also cause HTG and include thiazides, beta-blockers, oral estrogens, tamoxifen, OCPs, anti-retroviral protease inhibitors, atypical antipsychotics, isotretinoin, corticosteroids, bile acid-binding resins, and immunosuppressive agents such as sirolimus. Other causes of HTG include alcoholism and diets with high saturated fat or high glycemic index content. Individuals with HTG are typically treated with lifestyle changes and statin therapy to lower LDL-C. HTG is classified into three categories including, mild (TG level 150-199 mg / dL), high (TG 200-499 mg / dL), and very high (TG > 500 mg / dL) (National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) Guidelines). Reducing TG levels of below 150 mg / dL is critical for managing HTG. In some embodiments, HTG comprises a serum TG level of between about 150 mg / dL and about 199 mg / dL. In some embodiments, HTG comprises a serum TG level of between about 200 mg / dL and about 499 mg / dL. In some embodiments, HTG comprises a serum TG level of greater than or equal to about 500 mg / dL. Treatment for HTG includes but is not limited to fibrates (e.g., fenofibrate), omega-3 fatty acids (OM3FA), niacin, and cholesterol synthesis inhibitors (e.g., statins). Severe Hypertriglyceridemia In some embodiments, the medical disorder to be treated is Severe Hypertriglyceridemia (HTG). In some embodiments, Severe HTG comprises a serum TG level of between about 200 mg / dL and about 499 mg / dL. In some embodiments, Severe HTG comprises a serum TG level of greater than or equal to about 500 mg / dL. Severe HTG substantially increases the risk for pancreatitis and requires aggressive therapeutic intervention. Treatment for Severe HTG include but are not limited to omega-3 fatty acids (OM3FA). Metabolic Syndrome In some embodiments, the medical disorder to be treated is Metabolic Syndrome. Metabolic Syndrome is a complex medical disorder characterized by a suite of metabolic risk factors. These risk factors include but are not limited to obesity, hypertension, insulin resistance, glucose intolerance, prothombotic and / or proinflammatory state, and dyslipidemia. Subjects are typically diagnosed with Metabolic Syndrome if three of the following criteria are met: 1) obesity (waist circumference >35 in in women, >40 in in men); 2) low HDL levels (<50 mg / dL in women, <40 mg / dL in men); 3) high blood pressure (≥130 / 85 mmHg) or undergoing antihypertension medication treatment; 4) hypertriglyceridemia (TG levels ≥150 mg / dL); and 5) blood glucose levels ≥100 mg / DL). Treatment of a subject having a Metabolic Syndrome is focused on reducing one or more of the aforementioned criteria. Treatment for Metabolic Syndrome includes lifestyle modifications supplemented by therapies to manage complications which include but are not limited to cholesterol synthesis inhibitors (e.g., statins), fibrates, niacin, omega-3 fatty acids (OM3FA), and bariatric surgery. Mixed Dyslipidemia In some embodiments, the medical disorder to be treated is Mixed Dyslipidemia. Mixed Dyslipidemia is characterized by increased serum LDL-C and TG levels with low levels of HDL cholesterol. Between about 0.5%-9% of the population experience Mixed Dyslipidemia. Mixed Dyslipidemia is primarily caused by hepatic overproduction of very low density lipoprotein (VLDL) particles comprising both TG and LDL-C which contribute to the elevated LDL-C and TG levels. Mixed Dyslipidemia is often associated with dysfunctional lipoprotein lipase (LPL) which hydrolyzes TG from TRLs, VLDL, and chylomicrons. Treatment for Mixed Dyslipidemia includes lifestyle modifications supplemented by therapies to manage complications which include but are not limited to cholesterol synthesis inhibitors (e.g., HMG-CoA reductase inhibitors, statins), cholesterol absorption inhibitors (e.g., ezetimibe), PCSK9 inhibitors, icosapent ethyl, ATP citrate lyase inhibitors (e.g., bempedoic acid), bile acid sequestrants, fibrates, niacin, and aspirin. Myocardial Infarction In some embodiments, the medical disorder to be treated is Myocardial Infarction. Myocardial Infarction (MI) is usually referred to as a “heart attack” and is caused by acute blood flow stoppage of a coronary artery in the heart and necroses of the heart muscle. In the year of 2015, MI was mentioned as a contributing factor of 151,000 deaths based on data from the National Health Interview Survey (NHIS-CDC). According to the National Health and Nutrition Examination Survey (NHANES)-CDC 2011-2014 data, approximately 3% of adults older than 20- years of age in the United States experienced MI, with an estimated annual incidence of 605,000 new MI events and 200,000 recurrent MI events (Benjamin, E.J. et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 137(12):e67-e492(2018 Mar 20)). MI generally is caused by underlying coronary artery disease and results from a blood clot in the epicardial artery, although not all cases require a blood clot. MI can go undetected in some cases while in other cases MI can lead to sudden death (Thygesen, K. et al. Universal definition of myocardial infarction. Circulation.116(22):2634-2353(2007 Nov 27)). Extended oxygen loss in the myocardium can lead to myocardial cell death and necrosis (Reimer, K.A. et al. Pathobiology of acute myocardial ischemia: metabolic, functional and ultrastructural studies. Am J Cardiol. 52(2):72A-81A(1983 Jul 20)). Acute MI has a mortality rate of between about 5%-30% and the majority of deaths occur before arrival to the hospital. Within the first year of MI onset, there is an additional mortality rate of between about 5%-12%. Individuals having MI generally experience chest discomfort with or without dyspnea, nausea, and / or diaphoresis. Pain may radiate to the neck, jaw, shoulder, and / or arm. Diagnosis is generally made by electrocardiography (ECG) and the presence or absence of serologic markers. Individuals having MI are treated with medications including antiplatelet drugs, anticoagulants, nitrates, beta-blockers, statins, and reperfusion therapy. MI is clinically evaluated using clinical feature, ECG findings (resting 12 lead ECG), and cardiac biomarker (Cardiac troponins (I and T)) measurements, and imaging (echocardiography, cardiac MRI). Common risk factors associated with MI include smoking, abnormal lipid profile, abnormal blood apoB and / or apoA1 levels, hypertension, diabetes, obesity, poor diet, and physical inactivity with smoking and abnormal apolipoprotein levels showing the highest relationship with MI. The average age of first MI is 65.6-years for males and 72.0-years for females (Benjamin, E.J. et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation.137(12):e67-e492(2018 Mar 20)). Long-term therapeutic management of MI includes but is not limited to lipid-lowering treatments (e.g., statins), antithrombotic therapy (e.g., aspirin), ACE inhibitors, beta-blockers, anti- hypertensive therapy, mineralocorticoid receptor antagonist therapy, and glucose lowering therapy. Patients are also highly recommended to quit smoking and alter their weight via diet and alcohol consumption measures. Non-alcoholic fatty liver disease (NAFLD) In some embodiments, the medical disorder to be treated is Non-alcoholic fatty liver disease (NAFLD). NAFLD is a common cause of chronic liver disease, affecting about 24% of the United States population with prevalence continually increasing (Younossi, Z.M. et al. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology.64(1):73–84(2016)). Increased body size and Type 2 Diabetes remain among the most common risk factors for developing NAFLD. It is estimated that approximately 75% of overweight individuals and greater than 90% of severely obese individuals have NAFLD (Cotter, T.G. & Rinella, M. Nonalcoholic fatty liver disease 2020: the state of the disease. Gastroenterology. 158(7):1851–1864(2020); Machado, M. et al. Hepatic histology in obese patients undergoing bariatric surgery. Journal of Hepatology.45(4):600–606(2006)). Between about 33%-66% of individuals with Type 2 Diabetes have NAFLD (Younossi, Z.M. et al. Global epidemiology of nonalcoholic fatty liver disease— meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 64(1):73– 84(2016)). Individuals with NAFLD also carry an elevated risk of other health complications including Type 2 Diabetes, Metabolic Syndrome, high blood pressure, elevated cholesterol and TG serum levels, and cardiovascular disease (CVD), which is the most common cause of death for individuals with NAFLD. Individuals with NAFLD often meet one or more of the criteria of Metabolic Syndrome and exhibit complications including but not limited to hypertension, dyslipidemia, insulin resistance, and diabetes. NAFLD may eventually progress to fibrosis and cirrhosis of the liver. In some embodiments, the NAFLD is selected from Nonalcoholic fatty liver (NAFL) or Nonalcoholic steatohepatitis (NASH). Nonalcoholic fatty liver (NAFL) In some embodiments, the medical disorder to be treated is Nonalcoholic fatty liver (NAFL). NAFL is the non-inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) characterized by excess fat build-up in the liver and is not caused by alcoholism. Typically, NAFL is relatively benign and does not progress to liver damage or liver complications, but can cause pain due to liver enlargement. Nonalcoholic steatohepatitis (NASH) In some embodiments, the medical disorder to be treated is Nonalcoholic steatohepatitis (NASH). NASH is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by inflammation that is associated with disease progression of NAFLD and often requires liver transplantation. NASH is also associated with a higher risk of liver complications including cirrhosis of the liver and liver cancer, and increases a subject’s risk of dying from liver-related causes (Chalasani, N. et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 67(1):328–357(2018)). It is estimated that 20% of individuals with NASH will eventually develop cirrhosis of the liver. NASH carries a substantially elevated mortality rate compared with the general population or even patients with NAFLD not having this inflammatory subtype. NASH affects between about 1.5%-6.5% of the United States population and the prevalence is continually increasing. Risk factors for NASH include obesity, dyslipidemia, Type 2 Diabetes, and Metabolic Syndrome. While certain lab tests exist to characterize NAFLD and NASH, the only accepted diagnostic method for NASH is a liver biopsy. Currently, there are no FDA-approved therapies for NASH while dietary changes and exercise are recommended to improve health outcomes. Peripheral Vascular Disease (PVD) In some embodiments, the medical disorder to be treated is Peripheral Vascular Disease (PVD). PVD is a circulation disorder caused by narrowing, blockage, or spasms in blood vessel(s). PVD is most commonly caused by plaque build-up of the artery wall (atherosclerosis) which reduces blood flow to the limbs. Furthermore, blood clots can form on the artery walls to further constrict the vessel and block major arteries. Life-threatening complications are associated with PVD and include infection and amputations of digits and / or limbs. The most prevalent risk factors include age, heart disease, gender (male or post-menopausal women), and a family history of high cholesterol, high blood pressure, or PVD. Other risk factors associated with PVD include coronary artery disease, Diabetes, obesity, physical inactivity, and smoking. The most common early symptom of PVD is painful leg cramping that is triggered by exercise but alleviated by rest. Other PVD symptoms that, while common to other conditions, include skin temperature changes, weak limb pulses, gangrene, leg hair loss, impotence, poorly healing wounds, muscle weakness or numbness, digit pain, discoloration of extremities, restricted mobility, and thickened / opaque toenails. Therapeutic intervention of PVD is focused on the prevention rather than the treatment of PVD. Lifestyle changes including quitting smoking, losing weight, and reducing blood sugar levels have been demonstrated to decrease the progression of PVD and improve the quality of life. A subject should also not be administered any vasoconstricting medications. Current approaches to treatment include but are not limited to the use of cholesterol synthesis inhibitors (e.g., statins) in combination with either aspirin or the antiplatelet / vasodilator cilostazol. Post-Coronary Revascularization In some embodiments, the medical disorder to be treated is Post-Coronary Revascularization. Post-Coronary Revascularization is a condition following procedures to restore blood flow to areas of the heart lacking thereof to treat ischemia. Coronary artery disease is the most common cause of blood flow blockage with plaque build-up (atherosclerosis) being the main culprit. Two specific Coronary Revascularization procedures include Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). A PCI is a hollow tube-like catheter device that is inserted into a major blood vessel through to an artery to either administer either a balloon angioplasty, a stent, or brachytherapy to expand the artery and prevent narrowing (stenosis). CABG meanwhile comprises surgically accessing the heart to create a bypass vessel. Coronary Revascularization procedures are typically performed to treat the etiology of a previous heart attack or help to prevent a future heart attack. Coronary Revascularization is most commonly performed on individuals over the age of 65. Post-Coronary Revascularization involves an extended rehabilitation period to confirm proper function of the heart. While the recovery for PCI is short, the rehabilitation period for CABG can be weeks or even months. Worrisome symptoms during Post-Coronary Revascularization include angina, dyspnea, dizziness or lightheadedness, or fainting. Renal Artery Stenosis In some embodiments, the medical disorder to be treated is Renal Artery Stenosis. Renal Artery Stenosis is characterized by the narrowing of one or both of the renal arteries and is the major cause of hypertension. For example, of the 50 million Americans living with hypertension in the United States, Renal Artery Stenosis is believed to be the cause of 1%-10% of these cases (Ma, N. [Diagnostic value of contrast-enhanced ultrasound for accessory renal artery among patients suspected of renal artery stenosis]. Zhonghua Yi Xue Za Zhi.99(11):838-840(2019 Mar 19)). The most common causes of Renal Artery Stenosis are atherosclerosis (60%-90%) or fibromuscular dysplasia (10%-30%) (van Twist, D.J. et al. Pathophysiological differences between multifocal fibromuscular dysplasia and atherosclerotic renal artery stenosis. J Hypertens. 35(4):845-852(2017 Apr)). Other less common causes (<10%) include thromboembolic disease, arterials dissection, infrarenal aortic aneurysm, vasculitis, neurofibromatosis type 1, and retroperitoneal fibroses. Atherosclerosis is most common in men (over the age of 45) and usually involves the aortic orifice or the proximal 2 cm of the main renal artery. Fibromuscular dysplasia, meanwhile, occurs mainly in women (under the age of 50) and usually involves the middle and distal main retnal artery or intrarenal branches. Complications of Renal Artery Stenosis include chronic kidney disease (CKD) and end-stage renal disease (Eusébio, C.P. et al. Refractory ascites and graft dysfunction in early renal transplantation. J Bras Nefrol.41(4):570-574(2019 Oct-Dec)). Treatment for Renal Artery Stenosis includes lifestyle modification supplemented by therapies to manage complications that include but are not limited to antiplatelet therapies, cholesterol synthesis inhibitors (e.g., statins), ACE inhibitors, ARBs, calcium channel blockers, thiazide diuretics, and percutaneous revascularization. Stroke In some embodiments, the medical disorder to be treated is Stroke. Stroke is the second most common cause of death globally and a primary cause of disability with increasing prevalence in developing countries. Arterial occlusion causing ischemic stroke is the leading cause of a majority of stroke incidents. Interventions are time-sensitive focused on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy (EVT). Intravenous thrombolysis involves the use of an intravenous line or a catheter to inject thrombolytic agents to a site of blockage. EVT involves the removal of a blood clot from a blocked artery to restore blood flow. Use of reperfusion therapies help to reduce risk of disability if administered at an appropriate time. For example, intravenous thrombolysis reduces disability when administered 4.5 hours of stroke onset. EVT reduces disability in patients when administered within 6 hours of stroke onset. Approaches to prevent ischemic stroke overlap with those approaches in cardiovascular disorders. These include blood pressure control, cholesterol management, and antithrombotic medications. Certain other medications may be administered when applied to a particular stroke mechanism. For example, anticoagulation may be used for atrial fibrillation and carotid endarterectomy may be used for severe symptomatic carotid artery stenosis. Transient Ischemic Attack (TIA) In some embodiments, the medical disorder to be treated is Transient Ischemic Attack (TIA). TIA is a short-term (minutes to hour), sudden-onset neurological episode caused by a focal brain, spinal cord, or retinal ischemia (inadequate blood supply), without acute infarction or injury to the tissue. TIA episodes are estimated to total 500,000 per year in the United States, contributing to approximately 1.1 per 1000 in the general United States population. A TIA episode is often a warning of an impending ischemic stroke often within 48 hours of the TIA. Following a TIA episode, the risk of stroke within the next 3-months is about 20%, with about half of these strokes occurring within the next 48 hours after the episode. TIAs are often associated with focal neurologic deficits and / or speech abnormalities in a vascular territory due to an underlying cardiovascular disorder. Diagnosis and intervention of a TIA should be rapidly performed so as to prevent future strokes. Immediately initiated treatment modalities may reduce the risk of strokes or future TIA by at least 80% (Gennai, S. et al. [Transient Ischemic Attack: Limits and challenges of early management]. Presse Med.47(11-12 Pt 1):934-937(2018 Nov-Dec); Yousufuddin, M. et al. Predictors of Recurrent Hospitalizations and the Importance of These Hospitalizations for Subsequent Mortality After Incident Transient Ischemic Attack. J Stroke Cerebrovasc Dis. 28(1):167-174(2019 Jan); Kim, J. & Thrift, A.G. A Promising Skills-Based Intervention to Reduce Blood Pressure in Individuals With Stroke and Transient Ischemic Attack. JAMA Neurol. 76(1):13-14(2019 Jan 01)). Risk factors for TIA include age, obesity, smoking, alcoholism, poor diet, diabetes, hypertension, stress, and physical inactivity. A previous history of TIA or stroke substantially increases the risk of recurrent TIA or stroke (Navis, A. et al. Epidemiology and Outcomes of Ischemic Stroke and Transient Ischemic Attack in the Adult and Geriatric Population. J Stroke Cerebrovasc Dis. 28(1):84-89(2019 Jan); Cereda, C.W. & Olivot, J.M.. Emergency Department (ED) Triage for Transient Ischemic Attack (TIA). Curr Atheroscler Rep.20(11):56(2018 Sep 25)). Hypertension remains the highest risk factor for TIA. Scores used to asses subsequent risk of TIA or stroke, for example the ABCD2 score, rely on criteria including 1) age (older than 60-years); 2) blood pressure (>140 / 90 mmHg); 3) clinical presentation (spell or speech impairment); 4) TIA duration; and 5) diabetes mellitus. Treatment modalities include blood pressure control, statins, antiplatelet therapies, blood sugar control, diet, and exercise. Multi-modal regimens including a combination of diet, exercise, antiplatelet, stain, and antihypertensive therapy can greatly reduce the risk of subsequent stroke (Hackam D.G. & Spence, J.D. Combining multiple approaches for the secondary prevention of vascular events after stroke: a quantitative modeling study. Stroke.38(6):1881-1885(2007 Jun)). Prevention of Cardiovascular Disease in Individuals having one or more Comorbidities and / or Risk Factors In certain aspects, a treatment regimen is provided comprising the administration to a subject in need thereof of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof for the prevention of a medical disorder that can be treated with the apoB degrading compound in an individual having one or more comorbidities and / or risk factors. In some embodiments, the medical disorder to be prevented is selected from Renal Artery Stenosis, Atherosclerotic Cardiovascular Disease (ASCVD), Atherosclerosis, Aneurysm, Stroke, Transient Ischemic Attack, Coronary Heart Disease, Acute Coronary Syndrome, Myocardial Infarction, Angina Pectoris, Heart Failure, Coronary Artery Stenosis, Peripheral Vascular Disease, Post-Coronary Revascularization, ASCVD with Elevated Lipoprotein(a), Mixed Dyslipidemia, Hypercholesterolemia, Hyperlipidemia, Hypertriglyceridemia, Severe Hypertriglyceridemia, Familial Hypercholesterolemia (Type II Hyperlipoproteinemia) , Heterozygous Familial Hypercholesterolemia (HeFH) , Homozygous Familial Hypercholesterolemia (HoFH) , ASCVD Primary Prevention, ASCVD Primary Prevention with Elevated Lipoprotein(a), Familial Chylomicronemia Syndrome, Metabolic Syndrome, NAFLD, NASH, Complications of Type II Diabetes, or Complications of Chronic Kidney Disease. In some embodiments, the risk factor is selected from advanced age, obesity, smoking, alcoholism, poor diet, abnormal stress, prolonged physical inactivity, family history of cardiovascular disease, or a combination thereof. In some embodiments, the comorbidity is selected from diabetes, hypertension, Metabolic Syndrome, or a combination thereof. VI. COMBINATION TREATMENT In certain aspects, a treatment regimen is provided comprising the administration to a subject in need thereof of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent for the treatment of a medical disorder that can be treated with the apoB degrading compound. The combinations and / or alternations disclosed herein can be administered for beneficial, additive, or synergistic effect in the treatment of disorders, for example, a disorder of the liver. In some embodiments, an effective amount of an apoB degrading compound of the present invention is administered to a subject in need thereof in combination with an additional therapy for the treatment of a medical disorder that can be treated with the apoB degrading compound. In some embodiments, the additional therapy is selected from LDL apheresis, percutaneous revascularization, or bariatric surgery. In some embodiments, an effective amount of an apoB degrading compound of the present invention is administered to a subject in need thereof in combination with an additional therapeutic agent for the treatment of a medical disorder that can be treated with the apoB degrading compound. In some embodiments, the additional therapeutic agent is selected from an ACE inhibitor, an ACL inhibitor, an ANGPTL3 inhibitor, an angiotensin receptor neprilysin inhibitor (ARNI), an apoB inhibitor, an apoC-III inhibitor, an angiotensin II receptor blocker (ARB), an antithrombotic therapy, a beta-blocker, a bile sequestrant, a calcium channel blocker, a CETP inhibitor, a cholesterol synthesis inhibitor, a cholesterol absorption inhibitor, a fibrate, an Lp(a) inhibitor, a microsomal triglyceride transfer protein (MTP) inhibitor, omega-3 fatty acids (OM3FA), a PCSK9 inhibitor, a PPAR agonist, a vasodilator therapy, or a combination thereof. In some embodiments, the additional therapeutic agent is an ACE inhibitor. In some embodiments, the ACE inhibitor is selected from benazepril (Lotensin®), captopril, enalapril (Vasotec®), fosinopril, lisinopril (Zestril®), moexipril, perindopril, quinapril, ramipril (Altace®), trandolapril. In some embodiments, the additional therapeutic agent is an adenosine triphosphate-citrate lyase (ACL) inhibitor. In some embodiments, the ACL inhibitor is selected from bempedoic acid (NEXLETOL™) or bempedoic acid+ezetimibe (NEXLIZET™). In some embodiments, the additional therapeutic agent is an ANGPTL3 inhibitor. In some embodiments, the ANGPTL3 inhibitor is selected from evinacumab-dgnb (EVKEEZA™), AKCEA-ANGPTL3-LRX, VERVE-201, or ARO-ANG3. In some embodiments, the additional therapeutic agent is an angiotensin receptor neprilysin inhibitor (ARNI). In some embodiments, the ARNI is sacubitril / valsartan (Entresto®). In some embodiments, the additional therapeutic agent is an apoB inhibitor. In some embodiments, the apoB inhibitor is mipomersen (Kynamro®). In some embodiments, the additional therapeutic agent is an apoC-III inhibitor. In some embodiments, the apoC-III inhibitor is selected from ARO-APOC3 or Olezarsen. In some embodiments, the additional therapeutic agent is an angiotensin II receptor blocker (ARB). In some embodiments, the ARB is selected from azilsartan (Edarbi), candesartan (Atacand®), irbesartan (Avapro), losartan (Cozaar®), olmesartan (Benicar), telmisartan (Micardis®), or valsartan (Diovan®). In some embodiments, the additional therapeutic agent is an antithrombotic therapy. In some embodiments, the antithrombotic therapy is selected from an anticoagulant or antiplatelet agent. In some embodiments, the antithrombic agent is an anticoagulant. In some embodiments, the anticoagulant is selected from dabigatran (Pradaxa®), desirudin (Iprivask®), apixaban (Eliquis®), betrixaban (Bevyxxa™), edoxaban (Savaysa®), fondaparinux (Arixtra®), rivaroxaban (Xarelto®), heparin, dalteparin (Fragmin®), enoxaparin, tinzaparin (Innohep®), or warfarin. In some embodiments, the antithrombic agent is an antiplatelet agent. In some embodiments, the antiplatelet agent is selected from acetylsalicylic acid, a P2Y12 inhibitor, dipyridamole, cilostazol, dipyridamole / aspirin (Aggrenox), ticlopidine (Ticlid®), eptifibatide (Integrilin®). In some embodiments, the antiplatelet therapy is acetylsalicylic acid. In some embodiments, the acetylsalicylic acid is selected from aspirin, asaphen, entrophen, or novasen. In some embodiments, the antiplatelet therapy is a P2Y12 inhibitor. In some embodiments, the P2Y12 inhibitor is selected from clopidogrel (Plavix®), prasugrel (Effient®), or ticagrelor (Brilinta®). In some embodiments, the antithrombotic agent is selected from eminase (anistreplase), retavase (reteplase), streptase (streptokinase, kabikinase), t-PA (class of drugs that includes Activase), TNKase (tenecteplase), abbokinase, kinlytic (rokinase), or a combination thereof. In some embodiments, the additional therapeutic agent is a beta-blocker. In some embodiments, the beta-blocker is selected from acebutolol, atenolol (Tenormin), bisoprolol, metoprolol (Lopressor®, Toprol XL), nadolol (Corgard®), nebivolol (Bystolic®), or propranolol (Inderal® LA, InnoPran XL®). In some embodiments, the additional therapeutic agent is a bile sequestrant. In some embodiments, the bile sequestrant is selected from cholestyramine (Questran®, Prevalite®), colestipol (Colestid®, Flavored Colestid), colesevelam(Welchol®). In some embodiments, the additional therapeutic agent is a calcium channel blocker. In some embodiments, the calcium channel blocker is selected from amlodipine (Norvasc®), diltiazem (Cardizem®, Tiazac, others), felodipine, isradipine, nicardipine, nifedipine (Procardia®), nisoldipine (Sular®), or verapamil (Verelan®). In some embodiments, the additional therapeutic agent is a CETP inhibitor. In some embodiments, the CETP inhibitor is selected from anacetrapib, evacetrapib, dalcetrapib, obicetrapib. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the statin is selected from atorvastatin (Lipitor®), pitavastatin (Livalo®), lovastatin (Mevacor®, Altoprev ®), simvastatin (Zocor®), pravastatin (Pravachol®) fluvastatin (Lescol®, Lescol® XL), or rosuvastatin (Crestor®). Statins are also found in combination medications including: ADVICOR (lovastatin+niacin), CADUET (atorvastatin+amlopidine); selective cholesterol absorption inhibitors, ezetimibe (ZETIA®); a Lipid Lowering Therapy (LLT) fibrates or fibric acid derivatives, including gemfibrozil (LOPID), fenofibrate (ANTARA, LOFIBRA, TRICOR, TRIGLIDE) and clofibrate (ATROMID-S); a Resin (aka bile acid sequestrant or bile acid-binding drugs), cholestyramine (QUESTRAN, QUESTRAN LIGHT, PREVALITE, LOCHOLEST, LOCHOLEST LIGHT), cholestipol (CHOLESTID) and cholesevelan Hcl (WELCHOL) and / or a combination thereof, including but not limited to VYTORIN (simvastatin+ezetimibe). In some embodiments, the statin is rosuvastatin (Crestor®), which is administered orally once a day at a dose of about 5 mg to about 40 mg. In another embodiment, the statin is rosuvastatin (Crestor®), which is administered orally once a day at a dose of 5-40 mg. In some embodiments, the statin is atorvastatin (Lipitor®), which is administered orally once a day at a dose of about 10 mg to about 80 mg. In another embodiment, the statin is atorvastatin (Lipitor®), which is administered orally once a day at a dose of 10-80 mg. In some embodiments, the additional therapeutic agent is a cholesterol absorption inhibitor. In some embodiments, the cholesterol absorption inhibitor is ezetimibe (ZETIA®). In some embodiments, the ezetimibe (ZETIA®) is administered orally once a day at a dose of about 10 mg. In another embodiment, the ezetimibe (ZETIA®) is administered orally once a day at a dose of 10 mg. In some embodimetns, the cholesterol absorption inhibitor is simvastatin+ezetimibe (VYTORIN®). In some embodiments, the additional therapeutic agent is a fibrate. In some embodiments, the fibrate is selected from clofibrate (Atromid-S®), fenofibrate (TriCor®, Fibricor®, Lofibra®), or gemfibrozil (Lopid®). In some embodiments, the additional therapeutic agent is an Lp(a) inhibitor. In some embodiments, the Lp(a) inhibitor is selected from olpasiran or muvalaplin. In some embodiments, the additional therapeutic agent is a microsomal triglyceride transfer protein (MTP) inhibitor. In some embodiments, the MTP inhibitor is lomitapide (JUXTAPID®). In some embodiments, the lomitapide (JUXTAPID®) is administered orally once a day at a dose of about 5 mg to about 60 mg. In another embodiment, the lomitapide (JUXTAPID®) is administered orally once a day at a dose of 5-60 mg. In some embodiments, the lomitapide (JUXTAPID®) is administered orally once a day at a dose of about 20 mg. In another embodiment, the lomitapide (JUXTAPID®) is administered orally once a day at a dose of 20 mg. In some embodiments, the additional therapeutic agent is an omega-3 fatty acids (OM3FA). In some embodiments, the OM3FA is selected from alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA). In some embodiments, the additional therapeutic agent is a PCSK9 inhibitor. In some embodiments, the PCSK9 inhibitor is selected from alirocumab (PRALUENT®), evolocumab (AMG145, Repatha®), ALN-PCSsc (Inclisiran, Leqvio®), AT04A, MK-0616, EGF-A9, Pep2-8, LIB003, MG132, 7030B-C5, PF-06446846, AZD8233, VERVE-101, or R-IMPP. In some embodiments, the additional therapeutic agent is a PPAR agonist. In some embodiments, the PPAR agonist is selected from gemfibrozil (Lopid®), fenfibrate (Antara®, Lofibra®, Tricor®), or clofibrate (Atromid®). In some embodiments, the additional therapeutic agent is a vasodilator therapy. In some embodiments, the vasodilator therapy is selected from hydralazine (Apresoline®), minoxidil (Loniten®), or nitroglycerin (Nitrostat®). In certain aspects, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Hypercholesterolemia. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, a cholesterol absorption inhibitor, a bile acid sequestrant, LDL apheresis, an apoB inhibitor, an MTP inhibitor, a PCSK9 inhibitor, or a combination thereof. In some embodiments, the Hypercholesterolemia is Familial Hypercholesterolemia (Type II Hyperlipoproteinemia). In some embodiments, the Familial Hypercholesterolemia is selected from heterozygous familial Hypercholesterolemia (HeFH) or homozygous familial Hypercholesterolemia (HoFH). In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having ASCVD primary prevention. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from cholesterol synthesis inhibitor a cholesterol absorption inhibitor, a bile acid sequestrant, aPCSK9 inhibitor, an Lp(a) inhibitor, or a combination thereof. In some embodiments, the ASCVD primary prevention comprises ASCVD primary prevention with elevated Lipoprotein(a) (Lp(a)). In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having atherosclerosis. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, a beta-blocker, an ACE inhibitor, an angiotensin II receptor blocker (ARB), a calcium channel blocker, an MTP inhibitor, an apoB inhibitor, vasodilator therapy, a diuretic, or a combination thereof. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Atherosclerotic cardiovascular disease (ASCVD). In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, an MTP inhibitor, an apoB inhibitor, an Lp(a) inhibitor, or a combination thereof. In some embodiments, the ASDVD comprises ASCVD with elevated Lipoprotein(a) (Lp(a)). In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Acute Coronary Syndrome. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, a PCSK9 inhibitor, a cholesterol absorption inhibitor, an ACE inhibitor, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet therapy. In some embodiments, the antiplatelet therapy is acetylsalicylic acid. In some embodiments, the acetylsalicylic acid is aspirin. In some embodiments, the antithrombotic agent is an anticoagulant. In some embodiments, the anticoagulant is heparin. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having an Aneurysm. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a beta-blocker, a cholesterol synthesis inhibitor, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Angina Pectoris. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a beta-blocker, a cholesterol synthesis inhibitor, an ACE inhibitor, an ARB, ivabradine, a calcium channel blocker, a nitrate, nicorandil, ranolazine, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet therapy. In some embodiments, the antiplatelet therapy is acetylsalicylic acid. In some embodiments, the acetylsalicylic acid is aspirin. In some embodiments, the additional therapeutic agent is a calcium channel blocker. In some embodiments, the calcium channel blocker is selected from a non-dihydropyridine calcium channel blocker or a dihydropyridine calcium channel blocker. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Complications of Type II Diabetes. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a PPAR agonist, an oral hypoglycemic agent, an insulin sensitizer (e.g., metformin), a cholesterol synthesis inhibitor, a PCSK9 inhibitor, a cholesterol absorption inhibitor, an ACE inhibitor, an ARB, a non-sulfonylurea secretagogue, a thiazolidinedione, an alpha glucosidase inhibitor, insulin, a glucagon-like peptide 1 analog, a dipeptidyl peptidase-IV inhibitor, a sodium-glucose cotransporter 2 inhibitor, a 11ß-hydroxysteroid dehydrogenase 1 inhibitor, an insulin-releasing glucokinase activator, a pancreatic-G-protein-coupled fatty-acid- receptor agonist, a glucagon-receptor antagonist, a metabolic inhibitor of hepatic glucose output, quick-release bromocriptine, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is a cholesterol absorption inhibitor. In some embodiments, the cholesterol absorption inhibitor is ezetimibe. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Coronary Artery Stenosis. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from an antithrombotic agent, a cholesterol synthesis inhibitor, a hypertension therapy, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet therapy. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Coronary Heart Disease. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, a beta-blockers, an ACE inhibitor, a calcium channel blocker, a nitrate, ranolazine, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet therapy. In some embodiments, the antiplatelet therapy is acetylsalicylic acid. In some embodiments, the acetylsalicylic acid is aspirin. In some embodiments, the antiplatelet therapy is a P2Y12 inhibitor. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Familial Chylomicronemia Syndrome. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a beta-blocker, a thiazide diuretic, exogenous estrogen, or a combination thereof. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Heart Failure. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from an angiotensin receptor neprilysin inhibitor (ARNI), an ACE inhibitor, an ARB, a beta-blocker, hydralazine and nitrate, a mineralocorticoid receptor antagonist, a vasodilator therapy, or a combination thereof. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Hyperlipidemia. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a PPAR agonist, a cholesterol synthesis inhibitor, a cholesterol absorption inhibitor, a PCSK9 inhibitor, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is a cholesterol absorption inhibitor. In some embodiments, the cholesterol absorption inhibitor is ezetimibe. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Hypertriglyceridemia. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from PPAR agonist, a fibrate, an omega-3 fatty acid (OM3FA), niacin, a cholesterol synthesis inhibitor, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the Hypertriglyceridemia comprises Severe Hypertriglyceridemia. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Metabolic Syndrome. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, a fibrate, niacin, an omega-3 fatty acid (OM3FA), bariatric surgery, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Mixed Dyslipidemia. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, a CETP inhibitor, a cholesterol absorption inhibitor, a PCSK9 inhibitor, icosapent ethyl, an ACL inhibitor, a bile acid sequestrant, a fibrate, niacin, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is a cholesterol absorption inhibitor. In some embodiments, the cholesterol absorption inhibitor is ezetimibe. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet therapy. In some embodiments, the antiplatelet therapy is acetylsalicylic acid. In some embodiments, the acetylsalicylic acid is aspirin. In some embodiments, the additional therapeutic agent is an ACL inhibitor. In some embodiments, the ACL inhibitor is bempedoic acid. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Myocardial Infarction. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, an antithrombotic agent, an ACE inhibitor, a beta- blocker, an anti-hypertensive therapy, a mineralocorticoid receptor antagonist therapy, a glucose lowering therapy, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet therapy. In some embodiments, the antiplatelet therapy is acetylsalicylic acid. In some embodiments, the acetylsalicylic acid is aspirin. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Peripheral vascular disease. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, a vasodilator therapy, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet agent. In some embodiments, the antiplatelet agent is acetylsalicylic acid. In some embodiments, the acetylsalicylic acid is aspirin. In some embodiments, the antiplatelet agent is cilostazol. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Renal Artery Stenosis. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, an ACE inhibitor, an ARB, a calcium channel blocker, a thiazide diuretic, percutaneous revascularization, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet agent. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Stroke. In some embodiments, the at least one additional therapy and or therapeutic agent is an antithrombotic agent selected from eminase (anistreplase), retavase (reteplase), streptase (streptokinase, kabikinase), t-PA (class of drugs that includes Activase), TNKase (tenecteplase), abbokinase, kinlytic (rokinase), or a combination thereof. In another aspect, a treatment regimen is provided comprising the administration of an effective amount of an apoB degrading compound of the present invention or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof in combination or in alternation with at least one additional therapy and or therapeutic agent to a subject having Transient Ischemic Attack. In some embodiments, the at least one additional therapy and or therapeutic agent is selected from a cholesterol synthesis inhibitor, an antithrombotic agent, a beta-blocker, an ACE inhibitor, an ARB, or a combination thereof. In some embodiments, the additional therapeutic agent is a cholesterol synthesis inhibitor. In some embodiments, the cholesterol synthesis inhibitor is a statin. In some embodiments, the additional therapeutic agent is an antithrombotic agent. In some embodiments, the antithrombotic agent is an antiplatelet agent. Additional embodiments of the apoB degrading compound C1. A compound of Formula: I) II)

[0034] II); or a pharmaceutically acceptable salt thereof; wherein: ASGPR Binding Ligand is a compound selected from: ; Q2is selected from -O-, -N(R10)-, S, S(O), and S(O)2; R1and R5are independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-cyano, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, or C0-C6alkyl-O-S(O)2R3; R3at each occurrence is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, -OR8, and -NR8R9; R6and R7are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R8and R9are independently selected at each occurrence from hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocycle; R10is hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, C(O)R3, S(O)R3, C(S)R3, or S(O)2R3; R65, R66, and R67are independently selected at each occurrence from the group consisting of hydrogen, C0-C6alkyl-cyano, alkyl, alkenyl, alkynyl, haloalkyl, F, Cl, Br, I, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl- C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, and C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from R80; R80is independently selected at each instance from the group consisting of alkyl (including C1-C4alkyl), alkenyl (including C2-C4alkenyl), alkynyl (including C2-C4alkynyl), haloalkyl (including C1-C4haloalkyl), -OR6, F, Cl, Br, I, -NR6R7, heterocycle, heteroaryl, aryl, cyano, nitro, hydroxyl, azide, amide, -SR6, -S(O)(NR6)R3, -NR8C(O)R3, -C(O)NR6R7, and -C(O)R3; LinkerAand LinkerBare independently selected from: ; LinkerCis select ; LinkerDis sele ; R11, R12, R13, R , , , , , , at each occurrence selected from the group consisting of a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO2-, -S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R...

Claims

CLAIMS We Claim:

1. A compound of Formula: I) II);or a pharmaceutically acceptable salt thereof;wherein: ASGPR Binding Ligand is a moiety selected from:Q2is selected from -O-, -N(R10)-, S, S(O), and S(O)2;is heteroaryl or phenyl, each of which is optionally substituted with 1 or 2 substituents independently selected from R65; R1and R5are independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-cyano, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl-C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, or C0-C6alkyl-O-S(O)2R3; R3at each occurrence is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, -OR8, and -NR8R9; R6and R7are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R8and R9are independently selected at each occurrence from hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocycle; R10is hydrogen, alkyl, haloalkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycle, C(O)R3, S(O)R3, C(S)R3, or S(O)2R3; R65, R66, and R67are independently selected at each occurrence from the group consisting of hydrogen, C0-C6alkyl-cyano, alkyl, alkenyl, alkynyl, haloalkyl, F, Cl, Br, I, heterocycle, heterocycloalkyl, haloalkoxy, C0-C6alkyl-OR6, C0-C6alkyl-SR6, C0-C6alkyl-NR6R7, C0-C6alkyl- C(O)R3, C0-C6alkyl-S(O)R3, C0-C6alkyl-C(S)R3, C0-C6alkyl-S(O)2R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-N(R8)-S(O)R3, C0-C6alkyl-N(R8)-C(S)R3, C0-C6alkyl-N(R8)-S(O)2R3C0-C6alkyl-O-C(O)R3, C0-C6alkyl-O-S(O)R3, C0-C6alkyl-O-C(S)R3, -N=S(O)(R3)2, C0-C6alkylN3, and C0-C6alkyl-O-S(O)2R3, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from R80; R80is independently selected at each instance from the group consisting of C1-C4alkyl, C2- C4alkenyl, C2-C4alkynyl, C1-C4haloalkyl, -OR6, F, Cl, Br, I, -NR6R7, heterocycle, heteroaryl, aryl,cyano, nitro, hydroxyl, azide, amide, -SR6, -S(O)(NR6)R3, -NR8C(O)R3, -C(O)NR6R7, and -C(O)R3; LinkerAand LinkerBare independently selected from: ; ; ;at each occurrence selected from the group consisting of a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO2-, -S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, -P(O)(R3)O-, -P(O)(R3)-, a divalent residue of a natural or unnatural amino acid, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, -CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O- (CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, -[C(O)-CH2-O]n-, a divalent residue of a fatty acid, a divalent residue of an unsaturated and saturated mono- or di-carboxylic acid; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; n is independently selected at each instance from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, hydroxyl, alkoxy, azide, amino, cyano, -NR6R7, -NR8SO2R3, -NR8S(O)R3, haloalkyl, aryl, heteroaryl, and heterocycle; R22is independently at each occurrence selected from the group consisting of alkyl, -C(O)N-, -NC(O)-, -N-, -C(R21)-, -P(O)O-, -P(O)-, -P(O)(NR6R7)N-, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; R32is independently at each occurrence selected from the group consisting of alkyl, N+X-, -C-, alkenyl, haloalkyl, aryl, heterocycle, and heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; and X- is an anionic group; and ApoB Binding Ligand is a ligand that binds to apolipoprotein B.

2. The compound of claim 1, wherein R1is hydrogen.

3. The compound of claim 1 or claim 2, wherein the compound is of formula: ;4. The compound of claim 1 or claim 2, wherein the compound is of formula: ;or a p armaceu ca y accep a e sa ereo .

5. The compound of claim 1 or claim 2, wherein the compound is of formula: ;p y p .

6. The compound of any one of claims 1-5, wherein the ASGPR Binding Ligand is .

7. The compound of any, n the ASGPR Binding Ligand is .

8. The compound of any one of claims 1-5, wherein the ASGPR Binding Ligand is .

9. The compound of anyerein the ASGPR Binding Ligand is .

10. The compound of anyerein the ASGPR Binding Ligand is .

11. The compound of anyone o cams -, werein the ASGPR Binding Ligand is.

12. The compound of any oin the ASGPR Binding Ligand is .

13. The compound of anyin the ASGPR Binding Ligand is .

14. The compound of any one of claims 1-6, 8, 10, or 12, wherein isselected from: and15. The compound of any one of claims 1-5, wherein the ASGPR Binding Ligand is .

16. The compound of any one of claims 1-5, wherein the ASGPR Binding Ligand is .

17. The compound of any one of claims 1-5, wherein the ASGPR Binding Ligand is .

18. The compouPR Binding Ligand is .

19. The compou, PR Binding Ligand is selected from:

20. The compound of any one of claims 1-19, wherein ApoB Binding Ligand is selected from: , ndcycloalkyl; R101is independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, - C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-C3-C6cycloalkyl, C2- C6alkenyl, C2-C6alkynyl, and silyl; R102is independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, - C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-C3-C6cycloalkyl, C2- C6alkenyl, C2-C6alkynyl, and silyl; R103aand R103bare each independently selected from hydrogen, alkyl, haloalkyl, C0- C6alkyl-NR6R7, C0-C6alkyl-OR6, C0-C6alkyl-C(O)R3, C0-C6alkyl-N(R8)-C(O)R3, C0-C6alkyl-O- C(O)R3; R104and R105are independently selected at each occurrence from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, aryl, haloalkyl, heteroaryl, heterocycle, -alkyl-OR8, -alkyl-NR8R9, C(O)R3, S(O)R3, C(S)R3, and S(O)2R3; R104aand R104bare each independently selected from hydrogen and C1-4alkyl; R106is independently selected at each instance from hydrogen, halogen, and C1-C6alkyl;or together with the carbon they are attached to, two R106groups form a C3-C6cycloalkyl; R107,R107a, and R107bare independently selected at each instance from hydrogen, halogen, alkyl, haloalkyl, C0-C6alkyl-NR6R7, C0-C6alkyl-OR6, C0-C6alkyl-C(O)R3, C0-C6alkyl-N(R8)- C(O)R3, C0-C6alkyl-O-C(O)R3; or together with the carbon they are attached to, two R107groups form a C3-C6cycloalkyl; Z is C(O), S(O), S(O)2, or C(R107)2; QBis selected from bond, O, NR7, and C(R106)2; v is 1, 2, 3, or 4; w is 1, 2, 3, or 4; and R100is the attachment point to LinkerB, LinkerC, or LinkerD.

21. The compound of claim 20, wherein ApoB Binding Ligand is selected from: .. e compound o c a m 0, w ere n po nd ng gand s se ected rom: ,wherein R101aand R101bare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O- C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl; and R102aand R102bare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-C3- C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl.

23. The compound of claim 20, wherein ApoB Binding Ligand is selected from: ndw eren and are eac ndependent y se ected at eac occurrence rom ydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O- C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl; and R102aand R102bare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-C3- C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl.

24. The compound of claim 20, wherein ApoB Binding Ligand is selected from ,andR101aand R101bare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-C3- C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl; and R102aand R102bare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-C3- C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl.

25. The compound of claim 20, wherein ApoB Binding Ligand is selected from: , ,26. The compound of claim 20, wherein ApoB Binding Ligand is selected from: ,R101aand R101bare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-C3- C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl; and R102aand R102bare each independently selected at each occurrence from hydrogen, halogen, -C1-C6alkyl, -C1-C6haloalkyl, -C3-C6cycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-C3- C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, and silyl. .

27. The compound of claim 20, wherein ApoB Binding Ligand is selected from: , .

28. The compound of claim 24, wherein ApoB Binding Ligand is selected from ndnd30. The compound of claim 26, wherein ApoB Binding Ligand is selected from ,, .m , .. p , p g g ed from , , .

33. The compound of claim 20, wherein ApoB Binding Ligand is selected from , , .. y , ding Ligand is selected from: , 6);35. The compound of any one of claims 1-19, wherein ApoB Binding Ligand is . und of any one of claims 1-19, wherein ApoB Binding Ligand isselected fromRAB1and RAB2are independently selected from hydrogen, fluorine, alkyl, and haloalkyl; RAB3is hydrogen, -OH, alkyl, -NR6R7, or =O; RAB4, RAB5, RAB6are independently selected from hydrogen, fluorine, chlorine, bromine, alkyl, haloalkyl; and R100is the attachment point to LinkerB, LinkerCor LinkerD.

37. The compound of claim 36, wherein the compound is selected from: nd38. The compound of claim 36, wherein the compound is ,39. The compound of claim 38, wherein the compound isor a pharmaceutically acceptable salt thereof.

40. The compound of any one of claims 1-19, wherein ApoB Binding Ligand is of the formula: ;Z1and Z2are independently selected from CH and N; R109is selected from -C1-4alkyl-, -C2-6alkenyl-, -C0-6alkyl-S(O)2-, -C1-4acyl-, -C0-6alkyl- heteroaryl-, -C0-6alkyl-cycloalkyl, -C0-6alkyl-CO2-, -C0-6alkyl-C(O)NH-, and -C0-6alkyl-C1-4haloalkyl-; R110is selected from hydrogen, C1-6alkyl, or C1-3haloalkyl; R111is hydrogen, C1-3alkyl, fluoro, chloro, bromo, or C1-4haloalkyl; and R100is the attachment point to LinkerB, LinkerCor LinkerD.

41. The compound of any one of claims 1-19, wherein ApoB Binding Ligand is a peptide of SEQ ID NO: 1-47.

42. The compound of claim 41, wherein the ApoB Binding Ligand is selected from the group consisting of SEQ ID NO: 22, 23, 24, 25, 27, 28, 29, 30, 32, and 42.

43. The compound of any one of claims 1-19, wherein ApoB Binding Ligand is a peptide comprising 1, 2, or 3 of SEQ ID NO: 48-50 and 1, 2, or 3 of SEQ ID NO: 51-53.

44. The compound of any one of claims 1-19, wherein ApoB Binding Ligand is an antibody comprising the heavy chain of SEQ ID NO: 54 and the light chain sequence of SEQ ID NO:

55.

45. The compound of any one of claims 1-19, wherein the ApoB Binding Ligand is an antibody fragment comprising the variable heavy region (VH) amino acid sequence of SEQ ID NO:

56.

46. The compound of any one of claims 1-19, wherein the ApoB Binding Ligand is an antibody fragment comprising the variable light region (VL) amino acid sequence of SEQ ID NO: 57.

47. The compound of any one of claims 1-19, wherein the ApoB Binding Ligand is an aptamer selected from SEQ ID NO: 58-73.

48. The compound of any one of claims 1-47, wherein LinkerAis bond.

49. A compound selected from , , , ,, , , , ,, , , , nd; or a ph50. The compound of any one of claims 1-49, wherein LinkerBis: ; wherein:R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are independently at each occurrence selected from the group consisting of a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO2-, -S(O)-, -C(S)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, -P(O)(R3)O-, -P(O)(R3)-, a divalent residue of a natural or unnatural amino acid, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, -CH2CH2-[O-(CH2)2]n-O-, -CH2CH2-[O-(CH2)2]n-NR6-, -CH2CH2-[O- (CH2)2]n-, -[-(CH2)2-O-]n-, -[O-(CH2)2]n-, -[O-CH(CH3)C(O)]n-, -[C(O)-CH(CH3)-O]n-, -[O-CH2C(O)]n-, -[C(O)-CH2-O]n-, a divalent residue of a fatty acid, a divalent residue of an unsaturated and saturated mono- or di-carboxylic acid; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21; n is independently selected at each instance from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; R21is independently at each occurrence selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, F, Cl, Br, I, hydroxyl, alkoxy, azide, amino, cyano, -NR6R7, -NR8SO2R3, -NR8S(O)R3, haloalkyl, aryl, heteroaryl, and heterocycle.

51. The compound of any one of claims 1-50, wherein R16, R17, R18, R19, and R20are bond.

52. The compound of any one of claims 1-51, wherein R15, R16, R17, R18, R19, and R20are bond.

53. The compound of any one of claims 1-52, wherein R14, R15, R16, R17, R18, R19, and R20are bond.

54. The compound of any one of claims 1-53, wherein R13, R14, R15, R16, R17, R18, R19, and R20are bond.

55. The compound of any one of claims 1-54, wherein R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

56. The compound of any one of claims 1-55, wherein R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

57. The compound of any one of claims 1-50, wherein nine of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

58. The compound of any one of claims 1-50, wherein eight of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

59. The compound of any one of claims 1-50, wherein seven of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

60. The compound of any one of claims 1-50, wherein six of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

61. The compound of any one of claims 1-50, wherein five of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

62. The compound of any one of claims 1-50, wherein four of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

63. The compound of any one of claims 1-50, wherein three of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

64. The compound of any one of claims 1-50, wherein two of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20are bond.

65. The compound of any one of claims 1-50, wherein one of R11, R12, R13, R14, R15, R16, R17, R18, R19, and R20is bond.

66. The compound of any one of claims 1-50, wherein LinkerBisnd ; whewith 1, 2, 3, or 4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl.

67. The compound of claim 66, wherein R11, R12, R13, R15, R16, R18, R19, and R20are independently selected from bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NR6-, -NR6C(O)-, -O- , -S-, -NR6-, -C(R21R21)-, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, and - CH2CH2-[O-(CH2)2]n-O-.

68. The compound of any one of claims 1-50, wherein LinkerBis selected fromnd .

69. R19,20and R are independently selected from bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NR6-, -NR6C(O)-, -O-, -S-, -NR6-, -C(R21R21)-, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, and -CH2CH2-[O-(CH2)2]n-O-.

70. The compound of any one of claims 66-69, wherein R11is bond.

71. The compound of any one of claims 66-69, wherein R11is CH2.

72. The compound of any one of claims 66-69, wherein R11is -O-.

73. The compound of any one of claims 66-69, wherein R11is -C(O)NR6-.

74. The compound of any one of claims 66-69, wherein R11is -C(O)O-.

75. The compound of any one of claims 66-74, wherein R20is bond.

76. The compound of any one of claims 66-74, wherein R20is CH2.

77. The compound of any one of claims 66-74, wherein R20is -O-.

78. The compound of any one of claims 66-74, wherein R20is -C(O)NR6-.

79. The compound of any one of claims 66-74, wherein R20is -C(O)O-.

80. The compound of any one of claims 1-50, wherein LinkerBis selected fromnd .

81. Thecompound of any one of claims 66-80, wherein R is bond.

82. The compound of any one of claims 66-80, wherein R12is CH2.

83. The compound of any one of claims 66-80, wherein R12is -O-.

84. The compound of any one of claims 66-80, wherein R12is -C(O)NR6-.

85. The compound of any one of claims 66-80, wherein R12is -C(O)O-.

86. The compound of any one of claims 66-85, wherein R19is bond.

87. The compound of any one of claims 66-85, wherein R19is CH2.

88. The compound of any one of claims 66-85, wherein R19is -O-.

89. The compound of any one of claims 66-85, wherein R19is -C(O)NR6-.

90. The compound of any one of claims 66-85, wherein R19is -C(O)O-.

91. The compound of any one of claims 1-50, wherein LinkerBis selected fromnd ; whe with 1, 2, 3, or4 of any combination of halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, or cycloalkyl.

92. The compound of any one of claims 50-91, wherein aryl is phenyl.

93. The compound of any one of claims 50-92, wherein heteroaryl in LinkerBis s and94. The compound of claim 93, wherein heteroaryl in LinkerBis selected from is.ne of claims 1-96, wherein LinkerBis selected from,98. The compound of claim 1, of the formula:or100. The compound of claim 1, of the formula ,y .

101. The compound of claim 1, of the formula ,or a pharmaceutically acceptable salt thereof.

102. The compound of claim 1, of the formula ,or a pharmaceutically acceptable salt thereof.

103. The compound of claim 1, of the formula ,.

104. The compound of claim 1, of the formula ,or a pharmaceutically acceptable salt thereof.

105. The compound of claim 1, of the formula or ap y p .

106. The compound of claim 1, of the formula ,.

107. The compound of claim 1, of the formula ,or a pharmaceutically acceptable salt thereof.

108. The compound of claim 1, of the formula ,o a pa aceu ca y accepa e sa eeo.

109. The compound of claim 1, of the formula ,110. A pharmaceutical composition comprising a compound of any one of claims 1-109 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

111. A method for the treatment of a disorder sensitive to any one of the compounds of claims 1-109 comprising administering an effective amount of the compound of any one of claims 1-109 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof to a human.

112. The method of claim 111, wherein the disorder is selected from Renal Artery Stenosis, Atherosclerotic Cardiovascular Disease (ASCVD), Atherosclerosis, Aneurysm, Stroke, Transient Ischemic Attack, Coronary Heart Disease, Acute Coronary Syndrome, Myocardial Infarction, Angina Pectoris, Heart Failure, Coronary Artery Stenosis, Peripheral Vascular Disease, Post-Coronary Revascularization, ASCVD with Elevated Lipoprotein(a), Mixed Dyslipidemia, Hypercholesterolemia, Hyperlipidemia, Hypertriglyceridemia, Severe Hypertriglyceridemia, Familial Hypercholesterolemia (Type II Hyperlipoproteinemia) , Heterozygous Familial Hypercholesterolemia (HeFH) , Homozygous Familial Hypercholesterolemia (HoFH) , ASCVD Primary Prevention, ASCVD Primary Prevention with Elevated Lipoprotein(a), Familial Chylomicronemia Syndrome, Metabolic Syndrome, NAFLD, NASH, Complications of Type II Diabetes, or Complications of Chronic Kidney Disease.

113. The method of claim 111, wherein the disorder is selected from atherosclerosis, coronary artery disease, cerebrovascular disease, or peripheral artery disease, cardiovascular disease, familial hypercholesterolemia, and familial combined hyperlipidemia.

114. The method of any one of claims 111-113, wherein the human has an LDLR mutation.

115. The method of claim 114, wherein the LDLR mutation is a class I, class II, class III, class IV, class V, or class VI mutation.

116. The method of claim 115, wherein the LDLR mutation is C27W, C46S, A50S, S56P, R78C, W87G, C89Y, D90G, D90N, D90Y, Q92E, C95G, E101K, C116R, C134F, C134W, D139H, E140K, C143R, C148Y, C155Y, C160Y, D168H, D168N, D168Y, D172H, D172N, C173W, D175N, D175Y, S177L, C184W, C184Y, C197R, E201K, H211L, D221G, D221N, D221Y, C222Y, D224V, D227E, E228K, 32281, C231G, C243R, C248Y, Q254P, C255S, C261F, D266E, C276R, C276W, E277K, S286R, E288K, R300G, D301A, D301G, C302W, C302Y, D304N, S306L, C313Y, C318F, C318R, S326C, H327Y, C329F, C329Y, C338F, C338S, G343S, R350P, C352R, D356Y, C358Y, Q366R, C368R, C368Y, N370T, G373D, C379Y, D378P, C386Y, A399D, A399T, L401H, L401V, F403L, T404P, R406Q, E408K, T413M, L414R, D415G, R416Q, R416W, I423T, V429M, A431T, L432V, D433H, T434K, Y442H, I451T, T454N, V468I, R471G, L479P, D482H, W483R, D492N, V523M, P526S, P526T, G549D, N564H, N564S, R574C, R574H, W577G, W577R, W577S, D579N, D579Y, S584P, I585T, G592E, R595W, D601H, A606S, P608S, D622G, R633C, V639D, P649L, H656N, T659N, C667Y, P685L, C698Y, D700E, D700G, D707Y, E714K, T726I, T742I, V806D, R814Q, N825K, Y828C, G844D, or a combination thereof.

117. The method of claim 112, wherein the disorder is Familial Hypercholesterolemia (Type II Hyperlipoproteinemia).

118. The method of claim 117, wherein the disorder is Heterozygous Familial Hypercholesterolemia (HeFH).

119. The method of claim 117, wherein the disorder is Homozygous Familial Hypercholesterolemia (HoFH).

120. Use of a compound of any one of claims 1-109 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof in the manufacture of a medicament for the therapeutic treatment of a disorder sensitive to any one of the compounds of claims 1-109 in a human in need thereof.

121. Use of a compound of any one of claims 1-109 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof in the treatment of a disorder sensitive to any one of the compounds of claims 1-109 in a human in need thereof.

122. The use of claim 120 or 121, wherein the disorder is selected from Renal Artery Stenosis, Atherosclerotic Cardiovascular Disease (ASCVD), Atherosclerosis, Aneurysm, Stroke, Transient Ischemic Attack, Coronary Heart Disease, Acute Coronary Syndrome, MyocardialInfarction, Angina Pectoris, Heart Failure, Coronary Artery Stenosis, Peripheral Vascular Disease, Post-Coronary Revascularization, ASCVD with Elevated Lipoprotein(a), Mixed Dyslipidemia, Hypercholesterolemia, Hyperlipidemia, Hypertriglyceridemia, Severe Hypertriglyceridemia, Familial Hypercholesterolemia (Type II Hyperlipoproteinemia) , Heterozygous Familial Hypercholesterolemia (HeFH) , Homozygous Familial Hypercholesterolemia (HoFH) , ASCVD Primary Prevention, ASCVD Primary Prevention with Elevated Lipoprotein(a), Familial Chylomicronemia Syndrome, Metabolic Syndrome, NAFLD, NASH, Complications of Type II Diabetes, or Complications of Chronic Kidney Disease.

123. The use of claim 120 or 121, wherein the disorder is selected from atherosclerosis, coronary artery disease, cerebrovascular disease, or peripheral artery disease, cardiovascular disease, familial hypercholesterolemia, and familial combined hyperlipidemia.

124. The use of any one of claims 120-123, wherein the human has an LDLR mutation.

125. The use of claim 124, wherein the LDLR mutation is a class I, class II, class III, class IV, class V, or class VI mutation.

126. The use of claim 125, wherein the LDLR mutation is C27W, C46S, A50S, S56P, R78C, W87G, C89Y, D90G, D90N, D90Y, Q92E, C95G, E101K, C116R, C134F, C134W, D139H, E140K, C143R, C148Y, C155Y, C160Y, D168H, D168N, D168Y, D172H, D172N, C173W, D175N, D175Y, S177L, C184W, C184Y, C197R, E201K, H211L, D221G, D221N, D221Y, C222Y, D224V, D227E, E228K, 32281, C231G, C243R, C248Y, Q254P, C255S, C261F, D266E, C276R, C276W, E277K, S286R, E288K, R300G, D301A, D301G, C302W, C302Y, D304N, S306L, C313Y, C318F, C318R, S326C, H327Y, C329F, C329Y, C338F, C338S, G343S, R350P, C352R, D356Y, C358Y, Q366R, C368R, C368Y, N370T, G373D, C379Y, D378P, C386Y, A399D, A399T, L401H, L401V, F403L, T404P, R406Q, E408K, T413M, L414R, D415G, R416Q, R416W, I423T, V429M, A431T, L432V, D433H, T434K, Y442H, I451T, T454N, V468I, R471G, L479P, D482H, W483R, D492N, V523M, P526S, P526T, G549D, N564H, N564S, R574C, R574H, W577G, W577R, W577S, D579N, D579Y, S584P, I585T, G592E, R595W, D601H, A606S, P608S, D622G, R633C, V639D, P649L, H656N, T659N, C667Y, P685L, C698Y, D700E, D700G, D707Y, E714K, T726I, T742I, V806D, R814Q, N825K, Y828C, G844D, or a combination thereof.

127. The use of claim 122, wherein the disorder is Familial Hypercholesterolemia (Type II Hyperlipoproteinemia).

128. The use of claim 127, wherein the disorder is Heterozygous Familial Hypercholesterolemia (HeFH).

129. The use of claim 127, wherein the disorder is Homozygous Familial Hypercholesterolemia (HoFH).

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