Glycerol-3-phosphate-releasing compounds and use thereof to elevate fibroblast growth factor 21 expression

Abstract

Glycerol-3-phosphate-releasing compounds and pharmaceutical compositions comprising glycerol-3-phosphate-releasing compounds are used in methods of reducing sugar cravings, methods of reducing alcohol cravings, methods of treating diseases mediated by fibroblast growth factor 21, and methods of treating citrin deficiency.

Description

PATENT Docket No.: 048440-844001 WOGLYCEROL-3-PHOSPHATE-RELEASING COMPOUNDS AND USE THEREOF TO ELEVATE FIBROBLAST GROWTH FACTOR 21 EXPRESSIONCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to US Application No. 63 / 739,033 filed December 26, 2024, and US Application No. 63 / 725,059 filed November 26. 2024, the disclosures of which are incorporated by reference herein in their entirety.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

[0002] This invention was made with government support under R01 HL147545 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND

[0003] Fibroblast growth factor 21 (FGF21) is an endocrine factor that acts on multiple tissues, including the brain. By engaging with its coreceptor, [3-klotho (KLB), FGF21 inhibits ingestion of sweets and ethanol. The major site of FGF21 synthesis is the liver. In contrast, the sweet and ethanol-aversive actions of FGF21 have been mapped to KLB-expressing neurons in the ventromedial hypothalamus and the basolateral amygdala, respectively. Modified forms of FGF21 are being developed as drugs to increase metabolism, treat fatty liver, and dyslipidemia. There is a need in the art for new compounds and methods to increase metabolism, treat fatty liver disease, and dyslipidemia. The disclosure is directed to these, as well as other important ends.BRIEF SUMMARY

[0004] Provided herein are glycerol-3-phosphate-releasing compounds and pharmaceutical compositions comprising glycerol-3-phosphate-releasing compounds. The compounds are used in methods of treating diseases and conditions by elevating fibroblast grow th factor 21 expression. The glycerol-3-phosphate compounds may be any compound described herein, including pharmaceutically acceptable salts. In embodiments, the compounds are designed to release glycerol-3-phosphate.

[0005] These and other embodiments are described herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0006] FIG. 1 provides results for a gene expression study. AML12, a mouse hepatocyte line, was used to study gene expression in the liver. The Citrin gene. Slc25al3, was deleted in AML12 using CRISPR. When Slc25al3 was deleted, glycerol gained the activity of activating the ChREBP transcription factor and drove high expression of FGF21.

[0007] FIGS. 2A-2D show that glycerol activates the ChREBP transcription factor. Male C57BL / 6 mice were fed normal chow and given ad libitim access to either water or 5% glycerol for 48 hours. The data shows that glycerol activates the ChREBP transcription factor (FIG. 2A), drives transcription of LPK (FIG. 2B) and FGF21 (FIG. 2C), and leads to a doubling of FGF21 circulation into blood (FIG. 2D).

[0008] FIG. 3 provides an assement of the impact of ar l substituents in cycloSal prodrug strategies.

[0009] FIG. 4 provides a test of the '‘lock-in” cycloSal strategy.

[0010] FIG. 5 provides an assement of a multi-prodrug strategy'.

[0011] FIGS. 6A-6C show the design and general synthetic scheme for cyc / oSal glyc-3-P prodrug strategy. FIG. 6A: Mode of prodrug uptake by cells. FIG. 6B: General synthetic scheme for cycloSa\ glyc-3-P prodrugs. FIG. 6C: General synthetic scheme for cycloSal multi-prodrug strategy.

[0012] FIG. 7 shows G3P-releasing, FGF21 -inducing compounds (prodrugs).

[0013] FIGS. 8A-8B show G3P-releasing, FGF21 -inducing compounds (prodrugs).

[0014] FIGS. 9A-9B show that inactivation of NADH shuttle systems and glycerol induce FGF21 circulation. FIG.9A: Serum FGF21 from male mice of indicated genotypes were measured after two days with ad libitim access to food and water (control) or food and 5% (w / v) glycerol. The data show that Slc25a - / - Gpd2 - / - mice have elevated FGF21 and that each genotype has its FGF21 circulation elevated by glycerol. When data from the three mutant genotypes were combined (FIG. 9B), inactivation of one or more NADH shuttle systems clearly elevated FGF21 and the additive elevating effects of glycerol are also evident.

[0015] FIG. 10: Inactivation of NADH shuttle systems and glycerol drive a ChREBP transcription program. Hierarchical clustering of mean liver gene expression levels (fragments per kilobase of transcript per million mapped reads, FPKM) of select ChREBP target genes across four genotypes of mice exposed to either water (WAT) or glycerol (GLY).

[0016] FIGS. 11A-11C: NADH shuttle disruption elevates hepatic G3P. We performed quantitative metabolomics for (FIG. 11A) G3P and (FIG. 11B) hexose phosphates, and qualitative metabolomics for levels of (FIG. 11C) pentose phosphates in male wild-type (open circles) and mutant (filled squares) mouse livers lacking Slc25al3, Gpd2 and both Slc25al3 and Gpd2. The data show that G3P is elevated by deletion of NADH shuttle systems, whereas levels of hexose phosphates and pentose phosphates are unchanged.

[0017] FIGS. 12A-12F: the ChREBPa-specific isoform of ChREBP is activated in a manner that is coincident with G3P accumulation. FIG. 12A: HEK293T cells co-transfected withChREBPa, MLX, ChORE-luciferase and the indicated genetic constructs were assessed for ChORE-luciferase activity. The data show that LbNOX depresses, EcSTH increases and GPD1 greatly increases ChORE-luciferase activity. The relative levels of 137 metabolites were determined by LC-MS. By plotting ChORE-luciferase activity against each metabolite we show that G3P is highly correlated with ChREBPa-dependent ChORE-luciferase activity while (FIGS. 12B-12C) G6P and (FIG. 12D) are not. HEK293T cells co-transfected with ChREBPb, MLX, ChORE-luciferase and (FIG. 12E) either eGFP andZWVOXor (FIG. 12F) eGFP and EcSTH show that regulation is lost when the ChREBPa-specific N-terminus is deleted.

[0018] FIGS. 13A-13D: inductive reasoning of a potential G3P-ChREBP-FGF21 transcription system in CD hepatocytes. FIG. 13A: Two NADH shuttle systems link glycolysis to mitochondrial electron transfer. In glycolysis, fructose- 1,6-bisphosphate (F1,6BP) is split into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GA3P). In the GAPDH-dependent conversion of GA3P to 1,3-bisphosphogly cerate (1,3BPG), NAD+is reduced to NADH. To sustain glycolysis, the reducing equivalents from NADH are moved to mitochondria by the MAS and the GPDS. The MAS consists of two inner mitochondrial membrane antiporters plus isozymes of Asp aminotransferase (GOT1 and GOT2) and malate dehydrogenase (MDH1 and MDH2) on both sides of the membrane. SLC25A13, which is mutated in CD(2), moves Asp into cytosol against Glu into the mitochondrial matrix(7). SLC25A11 moves a-KG into cytosol against malate into the mitochondrial matrix (7 ). The direction of electron flow though the MAS is driven by the glycolytic formation of NADH in cytosol and the flow of electrons from NADH into the mitochondrial electron transport chain (METC). As a result of this electron flow, GOT1 receives a-KG and Asp, producing Glu plus oxaloacetate (OAA). Cytosolic MDH1 converts NADH and OAA to malate and NAD+, thereby provisioning malate to cany' reducing equivalents from glycolysis into the mitochondrial matrix and permitting continuous NAD -dependent glycolysis. Within the matrix, MDH2 captures the high energy electrons onto NAD+, forming NADH that initiates the METC at complex I. Production of OAA and mitochondrial entry of Glu drive mitochondrial GOT2 to run the reverse reaction of cytosolic GOT1. In the first step of the GPDS(74). a cytosolic G3P dehydrogenase encoded by Gpdl or Gpdll(84) converts NADH plus DHAP to glycerol-3-phosphate (G3P) plus NAD+. In the second step, G3P collides with the mitochondrial membrane-localized G3P dehydrogenase encoded by Gpd2 to regenerate DHAP with conversion of the GPD2 flavin adenine nucleotide (FAD) coenzyme to the reduced form, FADH2. So long as there is a functional METC and oxygen, FADH2 donates electrons to coenzyme Q to regenerate Gpd2 in its electron-accepting FAD form. FIG. 13B: With either mitochondrial insufficiency, disruption of the MAS, disruption of the GPDS, ethanolmetabolism or elevated glucose, cytosolic NADH is expected to rise, which would be expected to cause accumulation of G3P. FIG. 13C: Fructolysis, particularly in the presence of reductive stress, is predicted to elevate G3P. FIG. 13D: Triglyceride lipolysis is expected to produce elevated G3P and free fatty acids. G3P is proposed as the activating ligand of ChREBP, which would co-operate with activated PPARa (D) to activate transcription of FGF21 in a wide variety of conditions.DETAILED DESCRIPTION

[0019] Definitions

[0020] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art. See, e.g., Singleton et al., Dictionary of Microbiology and Molecular Biology. 2nd ed., J. Wiley & Sons (New York, NY 1994); Sambrook et al., Molecular Cloning, A Laboratory Manual, Cold Springs Harbor Press (Cold Springs Harbor, NY 1989). Any methods, devices and materials similar or equivalent to those described herein can be used in the practice of this disclosure. The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts. The following definitions are provided to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.

[0021] The term “fibroblast growth factor 21” or “FGF21” refers to an endocrine hormone that regulates energy homeostasis. In embodiments, FGF21 is induced in the liver in response to high carbohydrate levels. In embodiments, FGF21 enters circulation. In embodiments, FGF21 signals to the brain to suppress carbohydrate intake. In embodiments, genetic or pharmacological elevation of FGF21 levels suppresses the intake of simple sugars. In embodiments, genetic or pharmacological elevation of FGF21 levels suppresses the intake of sweeteners. In embodiments, genetic or pharmacological elevation of FGF21 levels does not suppress the intake of lipids. In embodiments, genetic or pharmacological elevation of FGF21 levels does not suppress the intake of proteins. In embodiments, FGF21 is a potentiator of leptin or leptin analog.

[0022] The term “glycerol compound” refers to glycerol and derivatives thereof. In embodiments, a “glycerol compound” is a compound described herein, glycerol, glycerol acetate, and glycerol-3-phosphate. In embodiments, a “glycerol compound” is a compound of Formula (I) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is a compound of Formula (II) or an embodiment thereof as described herein. Inembodiments, a “glycerol compound” is a compound of Formula (III) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is a compound of Formula (IV) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is a compound of Formula (V) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is a compound of Formula (VI) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is a compound of Formula (VII) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is a compound of Formula (VIIA) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is a compound of Formula (VIII) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is a compound of Formula (VIIIA) or an embodiment thereof as described herein. In embodiments, a “glycerol compound” is Compound A, Compound B, Compound C, Compound D, Compound E, Compound F, Compound G, Compound H. In embodiments, a “glycerol compound” is any compound described herein.

[0023] The terms “glycerol,” “glycerine,” “glycerin,” and “propane-1, 2, 3-triol” refer to a compound having the chemical structure:OH

[0024] The term “glycerol acetate” refers to a compound having the chemical structure:OR5wherein each R is independently hydrogen or -C(O)CH3, provided at least one R is -C(O)CH3. In embodiments, the glycerol acetate is glycerol monoacetin, glycerol diacetin, or glycerol triacetin. In embodiments, the glycerol acetate is glycerol monoacetin, wherein one R is -C(O)CH3 and two R are hydrogen. In embodiments, the glycerol acetate is glycerol diacetin, wherein two R are -C(O)CH3 and one R is hydrogen. In embodiments, the glycerol acetate is glycerol triacetin, wherein three R are -C(O)CH3.

[0025] The term “glycerol-3-phosphate” refers to a compound having the chemical structure:O II HO O | OH| OHOHIn embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal. In embodiments, the phosphate protecting group is N-acetyl-galactosamine, butyrate, acetate, or propionate. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, cycloSal, N-acetyl-galactosamine. butyrate, acetate, or propionate.

[0026] The term “butyrate” or “butyrate moiety” refers to a monovalent butyrate moiety having the structure:

[0027] The term “acetate” or “Ac” or “acetate moiety” refers to a monovalent acetate moiety' having the structure:

[0028] The term “acetoxyvinyl” or “acetoxyvinyl moiety” refers to structure:OAc

[0029] The term “propionate” or “propionate moiety” refers to a monovalent propionate moiety having the structure:

[0030] The term “N-acetyl-galactosamine moiety” refers to a monovalent moiety- having the structure:R101O OR1005R102Owherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond,-O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene. In embodiments, L5is a bond, -O-, or unsubstituted C1-12 heteroalkylene. In embodiments, L5is a bond, -O-, or unsubstituted C1-6 heteroalkylene. In embodiments, L5is -OCH2CH2- (wherein the oxygen is adjacent the heterocycle). In embodiments, R100, R101, and R102are hydrogen. In embodiments, two of R100, R101, and R102are hydrogen and one of R100, R101, and R102is -C(O)CH3. In embodiments, one of R100, R101, and R102is hydrogen and two of R100, R101, and R102are -C(O)CH3. In embodiments, R100. R101, and R102are -C(O)CH3. In embodiments, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2- (wherein the oxygen is adjacent the heterocycle). In embodiments, R100, R101, and R102are hydrogen, and L5is -OCH2CH2- (wherein the oxygen is adjacent the heterocycle).

[0031] The term “fenofibrate” and “fenofibrate moiety” refer to a monovalent fenofibrate moiety or monovalent fenofibric acid moiety having the structure of Fl or F2.

[0032] In embodiments, the term fenofibrate moiety refers to a moiety of the formula (Fl):

[0033] In embodiments, the term fenofibrate moiety refers to a moiety of the formula (F2):

[0034] The term “rosuvastatin” or “rosuvastatin moiety” refers to a monovalent rosuvastatin moiety having the formula:In embodiments, 1 or 2 of the -OH groups are -OAc groups. In embodiments, 1 -OH group is an -OAc group. In embodiments, 2 -OH groups are an -OAc group.

[0035] The term “acetyl-rosuvastatin” or “acetyl-rosuvastatin moiety” refers to a monovalent rosuvastatin moiety having the structure:NjlH3C-N Ni°'^ CH3

[0036] The term “fibrate” refers to a class of amphipathic carboxylic acids and esters. In embodiments, the fibrate is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety. With reference to the substituents for the compounds described herein, the term “fibrate” and “fibrate moiety” refer to a monovalent fibrate or monovalent fibrate acid that is linked or capable of being linked to the compounds described herein. In embodiments, the fibrate is in the form of an acid, such as fenofibric acid, clofibric acid, and the like. The skilled artisan would readily appreciate the chemical structure of a monovalent form of the fibrates described herein.

[0037] The term “statin” refers to HMG-CoA reductase inhibitors. In embodiments, the statin is atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. With reference to the substituents for the compounds described herein, the term “statin” and “statin moiety” refer to a monovalent statin that is linked or capable of being linked to the compounds described herein. The skilled artisan would readily appreciate the chemical structure of a monovalent form of the statins described herein.

[0038] The term “alkyl,” by itself or as part of another substituent, means, unless otherwise stated, a straight (i.e., unbranched) or branched carbon chain (or carbon), or combination thereof, which may be fully saturated, mono- or polyunsaturated and can include mono-, di- and multivalent radicals. The alkyl may include a designated number of carbons (e.g., Ci-Cio means one to ten carbons). Alkyl is an uncyclized chain. Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, methyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. In embodiments, Ci-6 alkyl is a Ci-4 alkyl. In embodiments, Ci-6 alkyl is a Ci-2 alkyl. In embodiments, Ci-6 alkyl(ene) is methyl, ethyl, propyl, iso-propyl, butyl, tert-butyl,or pentane. An unsaturated alkyl group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(l,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher homologs and isomers. An alkoxy is an alkyl attached to the remainder of the molecule via an oxygen linker (-O-). An alkyl moiety' may be an alkenyl moiety. An alkyl moiety may be an alkynyl moiety. An alkyl moiety may be fully saturated. An alkenyl may include more than one double bond and / or one or more triple bonds in addition to the one or more double bonds. An alkynyl may include more than one triple bond and / or one or more double bonds in addition to the one or more triple bonds. In embodiments, Ci-6 alkyl is a Ci-4 alkyl. In embodiments, Ci-6 alkyl is a C1-2 alkyl. In embodiments, Ci-6 alkyl(ene) is methyl, ethyl, propyl, iso-propyl, butyl, tert-butyl, or pentane.

[0039] The term “alkylene,” by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkyl, as exemplified by, e.g., -CH2CH2CH2CH2-. Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred herein. A “lower alkyl” or “lower alkylene” is a shorter chain alkyl or alkylene group, generally having eight or fewer carbon atoms. In embodiments, C1-6 alkylene is a C1-4 alkylene. In embodiments, C1-6 alkylene is a C1-2 alkylene. In embodiments, C1-6 alkylene is methylene, ethylene, propylene, iso-propylene, butylene, tertbutylene, or pentanene. The term “alkenylene,” by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkene.

[0040] A “substituent group,” as used herein (e.g., with reference to a substituted alkyl or substituted alkylene) means a group selected from the following moieties: (A) oxo, halogen, -CF3, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO2CI, -SO3H, -SO4H, -ONH2, -SO2NH2, -NHNH2, -NHC=(O)NHNH2. -NHC=(O)NH2, -NHSO2H, -NHC=(O)H, -NHC(O)-OH, -NHOH, -OCF3, -OCHF2, -NHSO2CH3, -N3, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and (B) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyd, aryl, heteroaryl, substituted with at least one substituent selected from: (i) oxo, halogen,-CF3. -CN, -OH, -NH2, -COOH. -CONH2. -NO2, -SH. -SO2CI, -SO3H, -SO4H, -SO2NH2.-NHNH2, -ONH2, -NHC=(O)NHNH2, -NHC=(O)NH2, -NHSO2H, -NHC=(O)H,-NHC(O)-OH, -NHOH, -OCF3, -OCHF2, -NHSO2CH3, -Ns, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and (ii) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, substituted with at least one substituent selected from: (a) oxo, halogen, -CF3,-CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO2CI, -SO3H, -SO4H, -SO2NH2, -NHNH2, -ONH2, -NHC=(O)NHNH2, -NHC=(O)NH2, -NHSO2H, -NHC=(O)H, -NHC(O)-OH, -NHOH, -OCF3, -OCHF2, -NHSO2CH3, -N, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and (b) alkyd, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, substituted with at least one substituent selected from: oxo, halogen, -CF3, -CN, -OH, -NH2, -COOH, -CONH2. -NO2, -SH, -SO2CI, -SO3H, -SO4H, -SO2NH2. -NHNH2, -ONH2, -NHC=(O)NHNH2, -NHC=(O)NH2, -NHSO2H, -NHC=(O)H, -NHC(O)-OH, -NHOH, -OCF3, -OCHF2, -NHSO2CH3, -N3, unsubstituted alkyl, unsubstituted heteroalky 1, unsubstituted cycloalky 1, unsubstituted heterocycloalkyl, unsubstituted ary l, unsubstituted heteroary l.

[0041] A “size-limited substituent” or “ size-limited substituent group,” as used herein, means a group selected from all of the substituents described above for a “substituent group,” wherein each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C20 alkyl, each substituted or unsubstituted heteroalky 1 is a substituted or unsubstituted 2 to 20 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C8 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3 to 8 membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted Ce-C 10 aryl, and each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5 to 10 membered heteroaryl.

[0042] A “lower substituent” or “ lower substituent group,” as used herein, means a group selected from all of the substituents described above for a “substituent group,” wherein each substituted or unsubstituted alkyl is a substituted or unsubstituted Ci-Cs alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2 to 8 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C7 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3 to 7 membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted Ce-Cio aryl, and each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5 to 9 membered heteroaiyl.

[0043] In some embodiments, each substituted group described in the compounds herein is substituted with at least one substituent group. More specifically, in some embodiments, each substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaiy l, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene described in the compounds herein are substituted with at least onesubstituent group. In other embodiments, at least one or all of these groups are substituted with at least one size-limited substituent group. In other embodiments, at least one or all of these groups are substituted with at least one lower substituent group.

[0044] In other embodiments of the compounds herein, each substituted or unsubstituted alkyl may be a substituted or unsubstituted C1-C20 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2 to 20 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C8 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3 to 8 membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted C6-C10 aryl, and / or each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5 to 10 membered heteroaryl. In some embodiments of the compounds herein, each substituted or unsubstituted alkylene is a substituted or unsubstituted C1-C20 alkylene, each substituted or unsubstituted heteroalkylene is a substituted or unsubstituted 2 to 20 membered heteroalkylene, each substituted or unsubstituted cycloalkylene is a substituted or unsubstituted C3-C8 cycloalkylene, each substituted or unsubstituted heterocycloalkylene is a substituted or unsubstituted 3 to 8 membered heterocycloalkylene, each substituted or unsubstituted arylene is a substituted or unsubstituted C6-C10 arylene, and / or each substituted or unsubstituted heteroarylene is a substituted or unsubstituted 5 to 10 membered heteroarylene.

[0045] In some embodiments, each substituted or unsubstituted alkyl is a substituted or unsubstituted Ci-Cs alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2 to 8 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C7 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3 to 7 membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted C6-C10 aryl, and / or each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5 to 9 membered heteroaryl. In some embodiments, each substituted or unsubstituted alkylene is a substituted or unsubstituted C1-C8 alkylene, each substituted or unsubstituted heteroalkylene is a substituted or unsubstituted 2 to 8 membered heteroalkylene, each substituted or unsubstituted cycloalkylene is a substituted or unsubstituted C3-C7 cycloalkylene, each substituted or unsubstituted heterocycloalkylene is a substituted or unsubstituted 3 to 7 membered heterocycloalkylene, each substituted or unsubstituted ary lene is a substituted or unsubstituted C6-C10 arylene, and / or each substituted or unsubstituted heteroarylene is a substituted or unsubstituted 5 to 9 membered heteroarylene. In some embodiments, the compound is a chemical species set forth in the Examples section below.

[0046] The term “disease mediated by fibroblast growth factor 21” or “disease mediated by FGF21 ’"refers to any disease caused (directly or indirectly) by low FGF21 activity (e.g., low FG21 activity relative to a control or low FG21 expression levels relative to a control). In embodiments, a disease mediated by fibroblast growth factor 21 is a metabolic disease. In embodiments, the control is a healthy patient or a population of healthy patients.

[0047] The term “a metabolic disease"’ refers to a disease caused by abnormal metabolism. In embodiments, the metabolic disease is related to low FGF21 activity (e.g., lower than a control). In embodiments, the control is a healthy subject or population of healthy subjects. In embodiments, the control is a subject without the metabolic disease or population of subjects without the metabolic disease. In embodiments, the disease is an eating disorder. In embodiments, the disease is diabetes. In embodiments, the disease is fatty liver. In embodiments, the disease is nonalcoholic steatohepatitis (NASH). In embodiments, the disease is hepatic encephalopathy. In embodiments, the disease is cirrhosis. In embodiments, the disease is dyslipidemia. In embodiments, the disease is hypercholesterolemia. In embodiments, the disease is hypertrigly ceridemia.

[0048] The term “metabolic syndrome” or “insulin resistance syndrome” refers to a collection of heart disease risk factors that increase the chance of developing heart disease, stroke, and diabetes in a subject. Risk factors include, but are not limited to, increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels.

[0049] The term "‘eating disorder” refers to a behavioral condition characterized by severe and persistent disturbance in eating behaviors and associated distressing thoughts and emotions. In embodiments, the eating disorder is obesity. In embodiments, the eating disorder is anorexia nervosa. In embodiments, the eating disorder is bulimia nervosa. In embodiments, the eating disorder is binge-eating disorder. In embodiments, the eating disorder is avoidant restrictive food intake disorder. In embodiments, the eating disorder is pica. In embodiments, the eating disorder is rumination disorder. In embodiments, the eating disorder is night eating syndrome. In embodiments, the eating disorder is orthorexia.

[0050] The term “obesity” refers to abnormal or excessive fat accumulation that presents a risk to health. A body mass index (BMI) over 25 is considered overweight, and a BMI over 30 is obese. In embodiments, raised BMI is a major risk factor for cardiovascular diseases.

[0051] The term “anorexia nervosa” refers to a condition where people avoid food, severely restrict food, or eat very small quantities of only certain foods.

[0052] The term “bulimia nervosa” refers to a condition where people have recurrent andfrequent episodes of eating unusually large amounts of food and feeling a lack of control over these episodes. In embodiments, overeating is followed by forced vomiting, excessive use of laxatives or diuretics, fasting, excessive exercise, or a combination of these behaviors.

[0053] The term '‘binge-eating disorder” refers to a condition where people lose control over their eating and have reoccurring episodes of eating unusually large amounts of food. Unlike bulimia nervosa, periods of binge-eating are not followed by purging, excessive exercise, or fasting. As a result, people with binge-eating disorder often are overweight or obese. Bingeeating disorder is the most common eating disorder in the U. S.

[0054] The term “avoidant restrictive food intake disorder” or “ARFID” refers to a condition where people limit the amount or type of food eaten. Unlike anorexia nervosa, people with ARFID do not have a distorted body image or extreme fear of gaining weight. In embodiments, people with ARFID lack appetite or interest in food.

[0055] The term “pica” refers to an eating disorder that involves eating things that are not considered food and that do not provide nutritional value. In embodiments, individuals with pica crave non-food substances such as ice, dirt, soil, chalk, soap, paper, hair, cloth, wool, pebbles, laundry detergent, or cornstarch.

[0056] The term '‘rumination disorder” refers to a condition in which a person regurgitates food they have previously chewed and swallowed, re-chews it, and then either re-swallows it or spits it out.

[0057] The term “night eating syndrome” refers to a condition where people frequently eat excessively at night, often after awakening from sleep.

[0058] The term “orthorexia” refers to a condition where people have an obsessive focus on healthy eating to an extent that disrupts their daily lives.

[0059] The term “fatty liver” or “hepatic steatosis” refers to the presence of an excessive amount of fat in the liver. In embodiments, people at risk of developing fatty liver are heavy drinkers. In embodiments, obesity may lead to fatty liver. In embodiments, the presence of fat in the liver is not associated with inflammation of the liver or damage to the liver cells. In embodiments, the hepatic steatosis is nonalcoholic steatohepatitis (NASH). In embodiments, NASH is associated with inflammation of the liver and liver cell damage.

[0060] The term '‘cirrhosis” refers to a chronic disease of the liver marked by degeneration of cells, inflammation, and fibrous thickening of tissue. In embodiments, cirrhosis is caused by alcoholism. In embodiments, cirrhosis is caused by alcoholic liver disease. In embodiments, cirrhosis is caused by nonalcoholic fatty liver disease. In embodiments, cirrhosis is caused by hepatitis. In embodiments, cirrhosis is caused by chronic hepatitis C. In embodiments, cirrhosisis caused by and chronic hepatitis B.

[0061] The term “hepatic encephalopathy'’ refers to a reversible syndrome of impaired brain function occurring in patients with advanced liver failure. In embodiments, hepatic encephalopathy is associated with acute liver failure. In embodiments, hepatic encephalopathy is associated with a portosystemic shunt that bypasses the liver. In embodiments, hepatic encephalopathy is associated with scarring and cirrhosis, which often occurs with chronic liver disease.

[0062] The term '‘alcohol use disorder” refers to an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. The term “alcohol use disorder” is defined in the American Psychiatric Association’s fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)

[0063] The term “diabetes” refers to a chronic health condition wherein the body does not produce insulin or is unable to use insulin to break down sugar, with resulting accumulation of sugar in the bloodstream. In embodiments, diabetes is type 2 diabetes. In embodiments, diabetes is gestational diabetes.

[0064] The term “citrin deficiency” refers to an inherited autosomal recessive metabolic condition. In embodiments, the citrin deficiency is caused by mutations in the gene encoding the mitochondrial transporter citrin. In embodiments, the citrin is a component of the mitochondrial malate-aspartate shuttle, which moves NADH from the cytosol into the mitochondria to generate adenosine triphosphate (ATP). In embodiments, the citrin is also required to supply aspartate to the cytosol, for proper functioning of the urea cycle. In embodiments, citrin is required for proper function of glycolysis. In embodiments, citrin is required for proper functionof gluconeogenesis. In embodiments, citrin is required for proper function of amino acid metabolism. In embodiments, citrin is required for proper function of the urea cycle. In embodiments, citrin is required for proper function of lipid metabolism. In embodiments, citrin deficiency is associated with a chronic energy deficit in the liver. In embodiments, citrin deficiency is associated with the inability of liver cells (hepatocytes) to efficiently utilize glucose and fatty acids as energy' sources to produce ATP.

[0065] The term “expression” or “expressed” as used herein in reference to a gene means the transcriptional and / or translational product of that gene. The level of expression of a DNA molecule in a cell may be determined on the basis of either the amount of corresponding mRNA that is present within the cell or the amount of protein encoded by that DNA produced by the cell. The level of expression of nucleic acid molecules may be detected by standard PCR or Northern blot methods well known in the art.

[0066] “Treating” or “treatment” as used herein (and as well-understood in the art) includes any approach for obtaining beneficial or desired results in a subject’s condition, including clinical results. Beneficial or desired clinical results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of the extent of a disease, stabilizing (i.e., not worsening) the state of disease, delaying or slow ing of disease progression, amelioration or palliation of the disease state, diminishment of the reoccurrence of disease, and remission, whether partial or total and whether detectable or undetectable. In other words, “treatment” as used herein includes any cure or amelioration of a disease. Treatment may inhibit the disease’s spread, relieve the disease’s symptoms, fully or partially remove the disease’s underlying cause, shorten a disease’s duration, or do a combination of these things. “Treating” does not include “preventing.”

[0067] The terms “patient,” “patient in need thereof,” “subject,” or “subject in need thereof’ refers to a living organism suffering from or prone to a disease or condition that can be treated by administration of a pharmaceutical composition as provided herein. Non-limiting examples include humans, other mammals, bovines, rats, mice, dogs, cats, monkeys, and other nonmammalian animals. In embodiments, a patient is human.

[0068] The term “administering” is used in accordance with its plain and ordinary meaning and includes oral administration, administration as a suppository, topical contact, intravenous, parenteral, intraperitoneal, intramuscular, intralesional, intrathecal, intranasal or subcutaneous administration, or the implantation of a slow-release device, e.g., a mini-osmotic pump, to a subject. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc. In embodiments, the administering does not include administration of any active agent other than the recited active agent. In embodiments, the administering includes simultaneous or sequential administration of another active agent in addition to the recited active agents.

[0069] Compounds

[0070] Provided herein are glycerol compounds. In embodiments, the glycerol compound is a compound of Formula (I) or a pharmaceutically acceptable salt thereof:wherein R1is hydrogen, butyrate, a fibrate moiety, or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety, or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen. In embodiments, R1is butyrate, a fibrate moiety, or a statin moiety; R2is butyrate, a fibrate moiety, or a statin moiety-; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety. In embodiments, the fibrate is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety. In embodiments, the statin is atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R1is hydrogen, butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R2is hydrogen, butyrate, bezafibrate, ciprofibrate, clinofibrate. clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1. R2. R3, and R4are not simultaneously hydrogen. In embodiments, R1is butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R2is butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety. In embodiments, R1and R2are not simultaneously hydrogen. In embodiments, the glycerol compound is a compound of Formula (I). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (I).

[0071] In embodiments, the glycerol compound is a compound of Formula (II) or a pharmaceutically acceptable salt thereof:OR!OR2(ii) wherein R1, R2, R3, and R4are each independently hydrogen, acetate, propionate, butyrate. N-acetyl galactosamine, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety7; and L1, L2, L3, and L4are each independently hydrogen or substituted or unsubstituted alkylene. In embodiments, the glycerol compound is a compound of Formula (II). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (II).

[0072] In embodiments, the glycerol compound is a compound of Formula (III) or a pharmaceutically acceptable salt thereof:(III) wherein R3and R4are each independently a fibrate moiety7, or a statin moiety7. In embodiments, R3and R4are each independently a fibrate moiety, or a statin moiety. In embodiments, the glycerol compound is a compound of Formula (III). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (III).

[0073] In embodiments, the glycerol compound is a compound of Formula (IV) or a pharmaceutically acceptable salt thereof:(IV) wherein R3and R4are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine moiety, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety; andL3and L4are each independently hydrogen or substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101. and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene. In embodiments, the glycerol compound is a compound of Formula (IV). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (IV).

[0074] In embodiments, the glycerol compound is a compound of Formula (V) or a pharmaceutically acceptable salt thereof:wherein R1and R2are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety: provided that R1and R2are not simultaneously hydrogen; L1and L2are each independently hydrogen or substituted or unsubstituted alkylene; and R6and R7are independently hydrogen, unsubstituted Ci-6 alkyl, -Cl, -F, -Br, -I, or acetoxyvinyl; wherein the N-acetyl galactosamine moiety7has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene. Inembodiments, the glycerol compound is a compound of Formula (V). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (V).

[0075] In embodiments, the glycerol compound is a compound of Formula (VI) or a pharmaceutically acceptable salt thereof:1" OR!(VI) wherein R1and R2are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine. N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety: provided that R1and R2are not simultaneously hydrogen; R5are each independently hydrogen or substituted or unsubstituted alkyl; and L1and L2are each independently hydrogen or substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.In embodiments, the glycerol compound is a compound of Formula (VI). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (VI).

[0076] In embodiments, the glycerol compound is a compound of Formula (VII) or a pharmaceutically acceptable salt thereof:(VII)wherein RAand RBare each independently a substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; L1and L2are each independently substituted or unsubstituted alkylene; Rcis independently hydrogen, halogen, substituted or unsubstituted alkyl, or acetoxyvinyl; n is 0, 1, 2, 3, or 4, wherein the N-acetyl galactosamine moiety7has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond.-O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene. In embodiments, the glycerol compound is a compound of Formula (VII). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (VII).

[0077] In embodiments, the glycerol compound is a compound of Formula (V1IA) or a pharmaceutically acceptable salt thereof:owherein RAand RBare each independently unsubstituted Ci-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety7; Rcis independently hydrogen, halogen, unsubstituted C1-6 alkyl, or acetoxyvinyl; and n is 0, 1, or 2. In embodiments, the glycerol compound is a compound of Formula (VIIA). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (VIIA).

[0078] In embodiments, the glycerol compound is a compound of Formula (VIII) or a pharmaceutically acceptable salt thereof:owherein RAand RBare each independently a substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety’; RDand REare each independently substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and L1, L2, L3, and L4are each independently substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101. and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene. In embodiments, the glycerol compound is a compound of Formula (VIII). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (VIII).

[0079] In embodiments, the glycerol compound is a compound of Formula (VIIIA) or a pharmaceutically acceptable salt thereof:wherein RAand RBare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and RDand REare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety. In embodiments, the glycerol compound is a compound of Formula (VIIIA). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (VIIIA).

[0080] In embodiments, the glycerol compound is a compound of Formula (IX) or a pharmaceutically acceptable salt thereof:R3,OOAc (IX), wherein R3and R4are independently a fibrate moiety, or a statin moiety. In embodiments, the glycerol compound is a compound of Formula (IX). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of the compound of Formula (IX).

[0081] In embodiments of the compounds described herein, R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety. In embodiments, this compound has the formula:

[0082] In embodiments, the compound has the formula:O

[0083] In embodiments of the compounds described herein, R1is rosuvastatin moiety; R2is fenofibrate; R3is butyrate; and R4is N-acetyl galactosamine moiety. In an embodiment, this compound has the formula:OO

[0084] In an embodiments, the compound has the formula:OO

[0085] Provided herein is Compound A or a pharmaceutically acceptable salt thereof.OAcIn embodiments, Compound A is free base form. In embodiments, Compound A is a pharmaceutically acceptable salt.

[0086] Provided herein is Compound B or a pharmaceutically acceptable salt thereof.In embodiments, Compound B is free base form. In embodiments, Compound B is a pharmaceutically acceptable salt.

[0087] Provided herein is Compound C or a pharmaceutically acceptable salt thereof.OAcIn embodiments. Compound C is free base form. In embodiments, Compound C is a pharmaceutically acceptable salt.

[0088] Provided herein is Compound D or a pharmaceutically acceptable salt thereof.o y oAcOAc In embodiments, Compound D is free base form. In embodiments, Compound D is a pharmaceutically acceptable salt.

[0089] Provided herein is Compound E or a pharmaceutically acceptable salt thereof.H3CnO O Y OACOAc In embodiments. Compound E is free base form. In embodiments, Compound E is a pharmaceutically acceptable salt.

[0090] Provided herein is Compound F or a pharmaceutically acceptable salt thereof.tBu is tert-butyl. In embodiments, Compound F is free base form. In embodiments, Compound F is a pharmaceutically acceptable salt.

[0091] Provided herein is Compound G or a pharmaceutically acceptable salt thereof.OAcOAcIn embodiments, Compound G is free base form. In embodiments, Compound G is a pharmaceutically acceptable salt.

[0092] Provided herein is Compound H or a pharmaceutically acceptable salt thereof.In embodiments, Compound H is free base form. In embodiments, Compound H is a pharmaceutically acceptable salt.

[0093] Substituents

[0094] In embodiments of the compounds described herein, R1and R2are each independently butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate. atorvastatin, fluvastatin, lovastatin, pitavastatin. pravastatin, rosuvastatin, or simvastatin. In embodiments, R1and R2are each independently bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate. atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R1and R2are each independently bezafibrate, ciprofibrate.clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety. In embodiments, R1and R2are each independently atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, one of R1and R2is a fibrate and the other of R1and R2is statin.

[0095] In embodiments of the compounds described herein, R1is butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin. lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R1is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R1is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety. In embodiments, R1is atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R1is butyrate. In embodiments, R1is bezafibrate moiety. In embodiments, R1is ciprofibrate moiety. In embodiments, R1is clinofibrate moiety. In embodiments, R1is clofibrate moiety. In embodiments, R1is clofibride. In embodiments. R1is fenofibrate moiety. In embodiments, the fenofibrate is fenofibric acid. In embodiments, R1is gemfibrozil. In embodiments, R1is nafenopin. In embodiments, R1is ronifibrate moiety. In embodiments, R1is simifibrate moiety. In embodiments, R1is atorvastatin. In embodiments, R1is fluvastatin. In embodiments, R1is lovastatin. In embodiments, R1is pitavastatin. In embodiments, R1is pravastatin. In embodiments, R1is rosuvastatin. In embodiments, R1is simvastatin.

[0096] In embodiments of the compounds described herein, R2is butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R2is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin. fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R2is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety. In embodiments, R2is atorvastatin, fluvastatin. lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R2is butyrate. In embodiments, R2is bezafibrate moiety. In embodiments, R2is ciprofibrate moiety. In embodiments, R2is clinofibrate moiety. In embodiments, R2is clofibrate moiety. In embodiments, R2is clofibride. In embodiments, R2is fenofibrate moiety. In embodiments, the fenofibrate is fenofibric acid. In embodiments, R2is gemfibrozil. In embodiments, R2is nafenopin. In embodiments, R2isronifibrate moiety. In embodiments, R2is simifibrate moiety. In embodiments, R2is atorvastatin. In embodiments, R2is fluvastatin. In embodiments, R2is lovastatin. In embodiments. R2is pitavastatin. In embodiments, R2is pravastatin. In embodiments, R2is rosuvastatin. In embodiments, R2is simvastatin.

[0097] In embodiments of the compounds described herein, R1is hydrogen, butyrate, or a fibrate; R2is hydrogen, butyrate, or a fibrate; R" is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen. In embodiments, R1is butyrate or a fibrate; R2is butyrate or a fibrate; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety. In embodiments, the fibrate is bezafibrate. ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety. In embodiments, R1is hydrogen, butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate; R2is hydrogen, butyrate, bezafibrate, ciprofibrate. clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate: R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen. In embodiments, R1is butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate; R2is butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1. R2. R3, and R4are not simultaneously hydrogen.

[0098] In embodiments of the compounds described herein, R1is hydrogen, butyrate, or a statin moiety: R2is hydrogen, butyrate, or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen. In embodiments, R1is butyrate or a statin moiety; R2is butyrate or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety. In embodiments, the statin is atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin. In embodiments, R1is hydrogen, butyrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R2is hydrogen, butyrate.atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen. In embodiments, R1is butyrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R2is butyrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety.

[0099] In embodiments of the compounds described herein, R1is hydrogen, butyrate, fenofibrate, or rosuvastatin moiety; R2is hydrogen, butyrate, fenofibrate, or rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen. In embodiments of the compound of Formulas (I)-(V), R1is hydrogen, butyrate, fenofibrate, or rosuvastatin moiety; R2is hydrogen, butyrate, fenofibrate, or rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1and R2are not simultaneously hydrogen. In embodiments, R1and R2are the same. In embodiments, R1and R2are different. In embodiments, R3and R4are the same. In embodiments, R3and R4are different. In embodiments, R1and R2are the same, and R3and R4are the same. In embodiments, R1and R2are the same, and R3and R4are different. In embodiments, R1and R2are different, and R3and R4are the same. In embodiments, R1and R2are different, and R3and R4are different.

[0100] In embodiments of the compounds described herein, R1is butyrate, fenofibrate, or rosuvastatin moiety; R2is butyrate, fenofibrate, or rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine

[0101] In embodiments of the compounds described herein R1is fenofibrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen. In embodiments, R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen. In embodiments. R1is fenofibrate; R2is fenofibrate; R3is N-acetyl galactosamine moiety; and R4is N-acetyl galactosamine moiety. In embodiments, R1is fenofibrate; R2is fenofibrate; R3is butyrate; and R4is butyrate. In embodiments, R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety. In embodiments, R1is butyrate; R2is butyrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety. In embodiments, R1is butyrate; R2is butyrate; R3is butyrate; and R4is butyrate. In embodiments,R1is butyrate; R2is butyrate; R3is hydrogen; and R4is hydrogen. In embodiments, R1is butyrate; R2is fenofibrate; R3is N-acetyl galactosamine moiety; and R4is hydrogen. In embodiments, R1is rosuvastatin moiety; R2is fenofibrate; R3is butyrate; and R4is N-acetyl galactosamine, and having the formula:

[0102] In embodiments of the compounds described herein, R1is butyrate; R2is butyrate; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety. In embodiments, R1is fenofibrate; R2is fenofibrate; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety. In embodiments, R1is rosuvastatin moiety; R2is rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety.

[0103] In embodiments of the compounds described herein, R1is butyrate; R2is butyrate; R3is hydrogen, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, butyrate, or N-acetyl galactosamine moiety. In embodiments, R1is fenofibrate; R2is fenofibrate; R3is hydrogen, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, butyrate, or N-acetyl galactosamine moiety. In embodiments, R1is rosuvastatin moiety; R2is rosuvastatin moiety; R3is hydrogen, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, butyrate, or N-acetyl galactosamine moiety.

[0104] In embodiments of the compounds described herein, R1is butyrate; R2is butyrate; R3is hydrogen; and R4is hydrogen, In embodiments, R1is fenofibrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen. In embodiments, R1is rosuvastatin moiety; R2is rosuvastatin moiety; R3is hydrogen; and R4is hydrogen.

[0105] In embodiments of the compounds described herein, R1is butyrate; R2is butyrate; R3is butyrate or N-acetyl galactosamine moiety; and R4is butyrate or N-acetyl galactosamine moiety. In embodiments, R1is fenofibrate; R2is fenofibrate; R3is butyrate or N-acetyl galactosamine moiety; and R4is butyrate or N-acetyl galactosamine moiety-. In embodiments, R1is rosuvastatin moiety; R2is rosuvastatin moiety; R" is butyrate or N-acetyl galactosamine moiety; and R4is butyrate or N-acetyl galactosamine moiety.

[0106] In embodiments of the compounds described herein, R1is butyrate; R2is butyrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety. In embodiments, R1is fenofibrate; R2is fenofibrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety. In embodiments, R1is rosuvastatin moiety; R2is rosuvastatin moiety; R3is hydrogen; and R4is N-acetyl galactosamine moiety.

[0107] In embodiments of the compounds described herein, R1is butyrate; R2is fenofibrate; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety. In embodiments, R1is butyrate; R2is rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety. In embodiments, R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen. In embodiments, R1is butyrate; R2is rosuvastatin moiety; R3is hydrogen; and R4is hydrogen.

[0108] In embodiments of the compounds described herein, L1, L2, L3, and L4are each independently hydrogen or substituted or unsubstituted alkylene. In embodiments of the compounds described herein, L1, L2, L3, and L4are each independently a bond or substituted or unsubstituted alkylene. In embodiments, L1, L2, L3, and L4are each independently unsubstituted Ci-io alkylene. In embodiments, L1, L2, L3, and L4are each independently unsubstituted Ci-6 alkylene. In embodiments, L1, L2, L3, and L4are each independently unsubstituted C1-5 alkylene. In embodiments, L1, L2, L3, and L4are each independently unsubstituted Ci-4 alkylene. In embodiments, L1, L2, L3, and L4are each independently unsubstituted C1-3 alkylene. In embodiments, L1, L2, L3, and L4are each independently unsubstituted C1-2 alkylene. In embodiments, L1, L2, L3, and L4are each independently methylene or ethylene. In embodiments, L1, L2, L3, and L4are methylene. In embodiments, L1, L2, L3, and L4are ethylene. In embodiments, L1and L2are methylene and L3and L4are ethylene.

[0109] In embodiments of the compounds described herein, RAand RBare each independently a substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, a statin moiety. In embodiments, RAand RBare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, a statin moiety. In embodiments, RAand RBare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, or butyrate. In embodiments, RAand RBare each independently a fibrate moiety or a statin moiety. In embodiments, RAand RBare each a fibrate moiety. In embodiments, RAand RBare each a statin moiety. In embodiments, RAand RBare each independently unsubstituted Ci-is alkyl group or N-acetyl galactosamine moiety. In embodiments, RAand RBare each independently unsubstituted Ci-18 alkyl group. In embodiments, RAand RBare each independently unsubstituted C1-12 alkyl group or N-acetyl galactosamine moiety. In embodiments, RAand RBare each independently unsubstituted C1-6 alkyl group or N-acetyl galactosamine moiety. In embodiments, RAand RBare each independently unsubstituted Ci-4alkyl group or N-acetyl galactosamine moiety. In embodiments, RAand RBare each independently unsubstituted C6-12 alkyl group or N-acetyl galactosamine moiety. In embodiments, RAand RBare each independently unsubstituted Cs-io alkyl group or N-acetyl galactosamine moiety. In embodiments, RAand RBare each independently unsubstituted C1-24 alkyl. In embodiments, RAand RBare each independently unsubstituted Ci-18 alkyl group. In embodiments, RAand RBare each independently unsubstituted C1-12 alkyl group. In embodiments, RAand RBare each independently unsubstituted C1-6 alkyl group. In embodiments, RAand RBare each independently unsubstituted Ci-4 alkyl group. In embodiments, RAand RBare each independently unsubstituted C6-24 alkyl group. In embodiments, RAand RBare each independently unsubstituted Ce-is alkyl group. In embodiments, RAand RBare each independently unsubstituted C6-12 alkyl group. In embodiments, RAand RBare each independently unsubstituted Cs-io alkyl group. In embodiments, RAand RBare each N-acetyl galactosamine moiety’. In embodiments, RAand RBare methyl.

[0110] In embodiments of the compounds described herein, Rcis independently hydrogen, halogen, substituted or unsubstituted alkyl, or acetoxyvinyl. In embodiments. Rcis independently hydrogen, halogen, substituted or unsubstituted C1-24 alkyl group, or acetoxyvinyl. In embodiments, Rcis hydrogen. In embodiments, Rcis independently hydrogen or halogen. In embodiments, Rcis halogen. In embodiments, Rcis substituted or unsubstituted Ci-24 alkyl group. In embodiments, Rcis substituted or unsubstituted C1-12 alkyl group. In embodiments, Rcis substituted or unsubstituted C1-6 alkyl group. In embodiments, Rcis substituted or unsubstituted C1-4 alkyl group. In embodiments, Rcis acetoxy vinyl.[OlH] In embodiments of the compounds described herein, n is 0, 1, 2, 3, or 4. In embodiments, n is 0. In embodiments n is 1. In embodiments n is 2. In embodiments, n is 3. In embodiments, n is 4. In embodiments, n is 0 or 1. In embodiments, n is 0, 1, or 2.

[0112] In embodiments of the compounds described herein, RDand REare each independently substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, buty rate, a fibrate moiety, or a statin moiety. In embodiments, RDand REare each independently substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety. In embodiments, RDand REare each independently substituted or unsubstituted C1-12 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety. In embodiments, RDand REare each independently substituted or unsubstituted C1-24 alkyl group. In embodiments. RDand REare each independently substituted or unsubstituted C1-12 alkyl group. In embodiments, RDandREare each independently unsubstituted C 1-24 alkyl group. In embodiments, RDand REare each independently unsubstituted C1-12 alkyl group. In embodiments. RDand REare each independently substituted or unsubstituted C1-24 alkyl group or N-acetyl galactosamine moiety. In embodiments, RDand REare each independently substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety. In embodiments, RDand REare each independently substituted or unsubstituted C1-24 alkyl group or N-acetyl galactosamine moiety. In embodiments, RDand REare each independently substituted or unsubstituted Ci -12 alkyl group or N-acetyl galactosamine moiety. In embodiments, RDand REare each independently unsubstituted C1-12 alkyl group or N-acetyl galactosamine moiety. In embodiments, RDand REare each independently N-acetyl galactosamine moiety. In embodiments, RDand REare each independently a fibrate moiety or a statin moiety. In embodiments, RDand REare each independently a fibrate moiety. In embodiments, RDand REare each independently a statin moiety'.

[0113] In embodiments of the compounds described herein, R5are each independently hydrogen or substituted or unsubstituted alkyl. In embodiments, R5is hydrogen. In embodiments, R5are each independently substituted or unsubstituted C1-6 alkyl. In embodiments, R5are each independently unsubstituted C1-6 alkyl. In embodiments, R3is methyl, ethyl, or propyl. In embodiments, R5is methyl. In embodiments, R5ethyl. In embodiments, R5is propyl.

[0114] In embodiments of the compounds described herein, R6and R7are independently hydrogen, unsubstituted C1-6 alkyl, -Cl, -F, -Br, -I, or acetoxy vinyl. In embodiments, R6is -CL -F, -Br, or -I. In embodiments, R6is -Br. In embodiments, R6is -Cl. In embodiments, R6is -F. In embodiments, R6is hydrogen. In embodiments, R6is unsubstituted C1-6 alkyl. In embodiments, R6is unsubstituted C1-4 alkyl. In embodiments, R6is unsubstituted C1-3 alkyl. In embodiments, R6is methyl. In embodiments, R6is ethyl. In embodiments, R6is tert-butyl. In embodiments, R6is acetoxyvinyl. In embodiments, R7is -Cl, -F, -Br, or -I. In embodiments, R7is -Cl. In embodiments, R7is -F. In embodiments, R7is -Br. In embodiments, R7is unsubstituted C1-6 alkyl. In embodiments, R7is unsubstituted C1-4 alkyl. In embodiments, R7is unsubstituted C1-3 alkyl. In embodiments, R7is methyl. In embodiments, R7is ethyl. In embodiments, R7is tertbutyl.

[0115] In embodiments of the compounds described herein, the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene. In embodiments, R100, R101. and R102are -C(O)CH₃, and L is -OCH2CH2-. In embodiments, R100, R101, and R102are -C(O)CH3. In embodiments, R100, R101, and R102are hydrogen. In embodiments, R100is hydrogen, R101is hydrogen, and R102is -C(O)CH3. In embodiments, R100is hydrogen, R101is -C(O)CH3, and R102is -C(O)CH3. In embodiments, R100is -C(O)CH3, R101is hydrogen, and R102is -C(O)CH3. In embodiments, R100is -C(O)CH3, R101is -C(O)CH3, and R102is hydrogen. In embodiments, L5is a bond. In embodiments, L5is a -O-. In embodiments, L5is a bond. In embodiments, L5is -OCH2CH2-. In embodiments, L5is a substituted or unsubstituted 2 to 6 membered heteroalkylene. In embodiments, L5is a substituted 2 to 6 membered heteroalkylene. In embodiments, L5is unsubstituted 2 to 6 membered heteroalkylene. In embodiments, L5is unsubstituted 2 to 4 membered heteroalkylene.

[0116] The term '‘pharmaceutically acceptable salt” is meant to include salts of the active compounds that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present disclosure contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds of the present disclosure contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic. or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, oxalic,methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see. for example, Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Science, 1977, 66, 1-19). Certain compounds may contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts.

[0117] Methods

[0118] Provided herein are methods of treating a disease or disorder mediated by fibroblast growth factor 21 comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the disease is a metabolic disease. In embodiments, the disease or disorder is craving sugar or ethanol (alcohol).

[0119] Provided herein are methods of reducing cravings for sugar in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, A-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0120] Provided herein are methods of reducing cravings for alcohol in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerolcompound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate. or cycloSal.

[0121] Provided herein are methods of treating overweight or obesity in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the method is for treating overweight in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the method is for treating obesity in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, overweight refers to a subject having a body mass index (BMI) of 22.0 to less than 30. In embodiments, overweight refers to a subject having a body mass index (BMI) of 23.0 to less than 30. In embodiments, overweight refers to a subject having a body mass index (BMI) of 24.0 to less than 30. In embodiments, overweight refers to a subject having a body mass index (BMI) of 25.0 to less than 30. In embodiments, obesity refers to a subject having a BMI of 30 or higher. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein(including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0122] Provided herein are methods of treating fatty liver disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. Provided herein are methods of treating nonalcoholic fatty liver disease (NAFLD) in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. Provided herein are methods of treating alcoholic fatty liver disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glyceroldiacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0123] Provided herein are methods of treating a metabolic disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the metabolic disease is diabetes, obesity, overweight, alcohol use disorder, an eating disorder, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, fatty7liver disease, nonalcoholic steatohepatitis, hepatic encephalopathy, or cirrhosis. In embodiments, the metabolic disease is diabetes, obesity, overweight, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, or an eating disorder. In embodiments, the metabolic disease is diabetes, obesity7, overweight, or dyslipidemia, hypercholesterolemia, or hypertriglyceridemia. In embodiments, the metabolic disease is diabetes, dyslipidemia, hypercholesterolemia, or hypertriglyceridemia. In embodiments, the metabolic disease is dyslipidemia, hypercholesterolemia, or hypertriglyceridemia. In embodiments, the eating disorder is anorexia nervosa, bulimia nervosa, binge-eating disorder, avoidant restrictive food intake disorder, pica, rumination disorder, night eating syndrome, or orthorexia. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, theglycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, 5-acyl-2-thioethyl, 4-acyl oxy benzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0124] Provided herein are methods of treating diabetes in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. Provided herein are methods of treating type 2 diabetes in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxy benzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0125] Provided herein are methods of treating alcohol use disorder in a subject in needthereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S’-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0126] Provided herein are methods of treating an eating disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the eating disorder is anorexia nervosa, bulimia nervosa, bingeeating disorder, avoidant restrictive food intake disorder, pica, rumination disorder, night eating syndrome, or orthorexia. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerolcompound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl. isopropyloxycarbonyloxymethyl, phosphoramidate. or cycloSal.

[0127] Provided herein are methods of treating anorexia nervosa in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxy benz l, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0128] Provided herein are methods of treating bulimia nervosa in a subject in need thereofcomprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S’-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0129] Provided herein are methods of treating binge-eating disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or morethereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0130] Provided herein are methods of treating avoidant restrictive food intake disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0131] Provided herein are methods of treating pica in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceuticallyacceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl. isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal

[0132] Provided herein are methods of treating rumination disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerolcompound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate. or cycloSal.

[0133] Provided herein are methods of treating night eating syndrome in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate. or cycloSal.

[0134] Provided herein are methods of treating orthorexia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodimentsthereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, 5-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0135] Provided herein are methods of treating nonalcoholic steatohepatitis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. Inembodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, 5-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal

[0136] Provided herein are methods of treating hepatic encephalopathy in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0137] Provided herein are methods of treating cirrhosis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as describedherein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphorami date, or cycloSal.

[0138] Provided herein are methods of treating dyslipidemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0139] Provided herein are methods of treating hypercholesterolemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0140] Provided herein are methods of treating hypertriglyceridemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound isglycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl, isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0141] Provided herein are methods of treating citrin deficiency in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a glycerol compound. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl,isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal.

[0142] Provided herein are methods of treating a disease mediated by fibroblast growth factor 21 in a subject in need thereof by administering to the subject an effective amount of an FGF21 inducer. In embodiments, the disease mediated by fibroblast growth factor 21 is a metabolic disease. In embodiments, the disease mediated by fibroblast growth factor 21 is a craving for alcohol or sugar. In embodiments, the FGF21 inducer is a glycerol compound as described herein, including embodiments thereof.

[0143] In embodiments, the methods provided herein further include administering to the subject a FGF21 inducer with a therapeutically effective amount of leptin or a leptin analog. In embodiments, the FGF21 inducer is a potentiator of leptin action. In embodiments, the leptin or leptin analog is administered together with the FGF21 inducer. In embodiments, the leptin or leptin analog and the FGF21 inducer are administered separately.

[0144] The present invention contemplates the administration of the compounds described herein, and compositions (e.g., pharmaceutical salts, pharmaceutical composition) thereof, in any appropriate manner. Suitable routes of administration include oral, parenteral (e.g., intramuscular, intravenous, subcutaneous (e.g., injection or implant), intraperitoneal, intraarticular, intraperitoneal, intracerebral (intraparenchymal) and intracerebroventricular), nasal, vaginal, sublingual, intraocular, rectal, topical (e.g., transdermal), buccal and inhalation. Depot injections, which are generally administered subcutaneously or intramuscularly, may also be utilized to release the compounds disclosed herein over a defined period of time. In embodiments, the administration is oral, lingual, sublingual, parenteral, rectal, topical, transdermal or pulmonary administration.

[0145] The compounds described herein may be administered to a subject in an effective amount that is dependent upon, for example, the goal of administration (e.g., the degree of resolution desired), the age, weight, sex, and health and physical condition of the subject to which the compound or composition is being administered, the route of administration, and the nature of the disease, disorder, condition or symptom thereof. The effective amount may also take into consideration the existence, nature, and extent of any adverse effects associated with the compound being administered. Effective amounts and dosage regimens can readily be determined from, for example, safety and dose-escalation trials, in vivo studies (e.g., animal models), and other methods known to the skilled artisan.

[0146] An “effective amount” is an amount sufficient for a compound to accomplish a stated purpose relative to the absence of the compound (e.g. achieve the effect for which it is administered, treat a disease, increase a signaling pathway, or reduce one or more symptoms of adisease). An example of an “effective amount” is an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, which could also be referred to as a “therapeutically effective amount.” A “reduction” of a symptom or symptoms (and grammatical equivalents of this phrase) means decreasing of the severity or frequency of the symptom(s), or elimination of the symptom(s). The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g.. Lieberman, Pharmaceutical Dosage Forms (vols. 1-3. 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins). For any compound described herein, the effective amount can be initially determined from cell culture assays. Target concentrations will be those concentrations of active compound that are capable of achieving the methods described herein, as measured using the methods described herein or known in the art. As is well known in the art, effective amounts for use in humans can also be determined from animal models. For example, an effective amount for humans can be formulated to achieve a concentration that has been found to be effective in animals. The effective amount in humans can be adjusted by monitoring compounds effectiveness and adjusting the dosage upwards or downwards.Adjusting the dose to achieve maximal efficacy in humans based on the methods described above and other methods is well within the capabilities of the ordinarily skilled artisan.

[0147] In embodiments of the methods described herein, the effective amount of the glycerol compound is about 1 mg to about 100 mg per day. In embodiments, the effective amount is about 1 mg to about 99 mg per day. In embodiments, the effective amount is about 1 mg to about 98 mg per day. In embodiments, the effective amount is about 1 mg to about 97 mg per day. In embodiments, the effective amount is about 1 mg to about 96 mg per day. In embodiments, the effective amount is about 1 mg to about 95 mg per day. In embodiments, the effective amount is about 1 mg to about 94 mg per day. In embodiments, the effective amount is about 1 mg to about 93 mg per day. In embodiments, the effective amount is about 1 mg to about 92 mg per day. In embodiments, the effective amount is about 1 mg to about 91 mg per day. In embodiments, the effective amount is about 1 mg to about 90 mg per day. In embodiments, the effective amount is about 1 mg to about 89 mg per day. In embodiments, the effective amount is about 1 mg to about 88 mg per day. In embodiments, the effective amount is about 1 mg to about 87 mg per day. In embodiments, the effective amount is about 1 mg to about 86 mg per day. In embodiments, the effective amount is about 1 mg to about 85 mg per day. In embodiments, the effective amount is about 1 mg to about 84 mg per day. Inembodiments, the effective amount is about 1 mg to about 83 mg per day. In embodiments, the effective amount is about 1 mg to about 82 mg per day. In embodiments, the effective amount is about 1 mg to about 81 mg per day. In embodiments, the effective amount is about 1 mg to about 80 mg per day. In embodiments, the effective amount is about 1 mg to about 79 mg per day. In embodiments, the effective amount is about 1 mg to about 78 mg per day. In embodiments, the effective amount is about 1 mg to about 77 mg per day. In embodiments, the effective amount is about 1 mg to about 76 mg per day. In embodiments, the effective amount is about 1 mg to about 75 mg per day. In embodiments, the effective amount is about 1 mg to about 74 mg per day. In embodiments, the effective amount is about 1 mg to about 73 mg per day. In embodiments, the effective amount is about 1 mg to about 72 mg per day. In embodiments, the effective amount is about 1 mg to about 71 mg per day. In embodiments, the effective amount is about 1 mg to about 70 mg per day. In embodiments, the effective amount is about 1 mg to about 69 mg per day. In embodiments, the effective amount is about 1 mg to about 68 mg per day. In embodiments, the effective amount is about 1 mg to about 67 mg per day. In embodiments, the effective amount is about 1 mg to about 66 mg per day. In embodiments, the effective amount is about 1 mg to about 65 mg per day. In embodiments, the effective amount is about 1 mg to about 64 mg per day. In embodiments, the effective amount is about 1 mg to about 63 mg per day. In embodiments, the effective amount is about 1 mg to about 62 mg per day. In embodiments, the effective amount is about 1 mg to about 61 mg per day. In embodiments, the effective amount is about 1 mg to about 60 mg per day. In embodiments, the effective amount is about 1 mg to about 59 mg per day. In embodiments, the effective amount is about 1 mg to about 58 mg per day. In embodiments, the effective amount is about 1 mg to about 57 mg per day. In embodiments, the effective amount is about 1 mg to about 56 mg per day. In embodiments, the effective amount is about 1 mg to about 55 mg per day. In embodiments, the effective amount is about 1 mg to about 54 mg per day. In embodiments, the effective amount is about 1 mg to about 53 mg per day. In embodiments, the effective amount is about 1 mg to about 52 mg per day. In embodiments, the effective amount is about 1 mg to about 51 mg per day. In embodiments, the effective amount is about 1 mg to about 50 mg per day. In embodiments, the effective amount is about 1 mg to about 49 mg per day. In embodiments, the effective amount is about 1 mg to about 48 mg per day. In embodiments, the effective amount is about 1 mg to about 47 mg per day. In embodiments, the effective amount is about 1 mg to about 46 mg per day. In embodiments, the effective amount is about 1 mg to about 45 mg per day. In embodiments, the effective amount is about 1 mg to about 44 mg per day. In embodiments, the effective amount is about 1 mg to about 43 mg perday. In embodiments, the effective amount is about 1 mg to about 42 mg per day. In embodiments, the effective amount is about 1 mg to about 41 mg per day. In embodiments, the effective amount is about 1 mg to about 40 mg per day. In embodiments, the effective amount is about 1 mg to about 39 mg per day. In embodiments, the effective amount is about 1 mg to about 38 mg per day. In embodiments, the effective amount is about 1 mg to about 37 mg per day. In embodiments, the effective amount is about 1 mg to about 36 mg per day. In embodiments, the effective amount is about 1 mg to about 35 mg per day. In embodiments, the effective amount is about 1 mg to about 34 mg per day. In embodiments, the effective amount is about 1 mg to about 33 mg per day. In embodiments, the effective amount is about 1 mg to about 32 mg per day. In embodiments, the effective amount is about 1 mg to about 31 mg per day. In embodiments, the effective amount is about 1 mg to about 30 mg per day. In embodiments, the effective amount is about 1 mg to about 29 mg per day. In embodiments, the effective amount is about 1 mg to about 28 mg per day. In embodiments, the effective amount is about 1 mg to about 27 mg per day. In embodiments, the effective amount is about 1 mg to about 26 mg per day. In embodiments, the effective amount is about 1 mg to about 25 mg per day. In embodiments, the lower amount in each of the ranges described herein is 2 mg. In embodiments, the lower amount in each of the ranges described herein is 3 mg. In embodiments, the lower amount in each of the ranges described herein is 4 mg.

[0148] In embodiments of the methods described herein, the effective amount of the glycerol compound is about 5 mg to about 100 mg per day. In embodiments, the effective amount is about 5 mg to about 99 mg per day. In embodiments, the effective amount is about 5 mg to about 98 mg per day. In embodiments, the effective amount is about 5 mg to about 97 mg per day. In embodiments, the effective amount is about 5 mg to about 96 mg per day. In embodiments, the effective amount is about 5 mg to about 95 mg per day. In embodiments, the effective amount is about 5 mg to about 94 mg per day. In embodiments, the effective amount is about 5 mg to about 93 mg per day. In embodiments, the effective amount is about 5 mg to about 92 mg per day. In embodiments, the effective amount is about 5 mg to about 91 mg per day. In embodiments, the effective amount is about 5 mg to about 90 mg per day. In embodiments, the effective amount is about 5 mg to about 89 mg per day. In embodiments, the effective amount is about 5 mg to about 88 mg per day. In embodiments, the effective amount is about 5 mg to about 87 mg per day. In embodiments, the effective amount is about 5 mg to about 86 mg per day. In embodiments, the effective amount is about 5 mg to about 85 mg per day. In embodiments, the effective amount is about 5 mg to about 84 mg per day. In embodiments, the effective amount is about 5 mg to about 83 mg per day. In embodiments, theeffective amount is about 5 mg to about 82 mg per day. In embodiments, the effective amount is about 5 mg to about 81 mg per day. In embodiments, the effective amount is about 5 mg to about 80 mg per day. In embodiments, the effective amount is about 5 mg to about 79 mg per day. In embodiments, the effective amount is about 5 mg to about 78 mg per day. In embodiments, the effective amount is about 5 mg to about 77 mg per day. In embodiments, the effective amount is about 5 mg to about 76 mg per day. In embodiments, the effective amount is about 5 mg to about 75 mg per day. In embodiments, the effective amount is about 5 mg to about 74 mg per day. In embodiments, the effective amount is about 5 mg to about 73 mg per day. In embodiments, the effective amount is about 5 mg to about 72 mg per day. In embodiments, the effective amount is about 5 mg to about 71 mg per day. In embodiments, the effective amount is about 5 mg to about 70 mg per day. In embodiments, the effective amount is about 5 mg to about 69 mg per day. In embodiments, the effective amount is about 5 mg to about 68 mg per day. In embodiments, the effective amount is about 5 mg to about 67 mg per day. In embodiments, the effective amount is about 5 mg to about 66 mg per day. In embodiments, the effective amount is about 5 mg to about 65 mg per day. In embodiments, the effective amount is about 5 mg to about 64 mg per day. In embodiments, the effective amount is about 5 mg to about 63 mg per day. In embodiments, the effective amount is about 5 mg to about 62 mg per day. In embodiments, the effective amount is about 5 mg to about 61 mg per day. In embodiments, the effective amount is about 5 mg to about 60 mg per day. In embodiments, the effective amount is about 5 mg to about 59 mg per day. In embodiments, the effective amount is about 5 mg to about 58 mg per day. In embodiments, the effective amount is about 5 mg to about 57 mg per day. In embodiments, the effective amount is about 5 mg to about 56 mg per day. In embodiments, the effective amount is about 5 mg to about 55 mg per day. In embodiments, the effective amount is about 5 mg to about 54 mg per day. In embodiments, the effective amount is about 5 mg to about 53 mg per day. In embodiments, the effective amount is about 5 mg to about 52 mg per day. In embodiments, the effective amount is about 5 mg to about 51 mg per day. In embodiments, the effective amount is about 5 mg to about 50 mg per day. In embodiments, the effective amount is about 5 mg to about 49 mg per day. In embodiments, the effective amount is about 5 mg to about 48 mg per day. In embodiments, the effective amount is about 5 mg to about 47 mg per day. In embodiments, the effective amount is about 5 mg to about 46 mg per day. In embodiments, the effective amount is about 5 mg to about 45 mg per day. In embodiments, the effective amount is about 5 mg to about 44 mg per day. In embodiments, the effective amount is about 5 mg to about 43 mg per day. In embodiments, the effective amount is about 5 mg to about 42 mg per day. Inembodiments, the effective amount is about 5 mg to about 41 mg per day. In embodiments, the effective amount is about 5 mg to about 40 mg per day. In embodiments, the effective amount is about 5 mg to about 39 mg per day. In embodiments, the effective amount is about 5 mg to about 38 mg per day. In embodiments, the effective amount is about 5 mg to about 37 mg per day. In embodiments, the effective amount is about 5 mg to about 36 mg per day. In embodiments, the effective amount is about 5 mg to about 35 mg per day. In embodiments, the effective amount is about 5 mg to about 34 mg per day. In embodiments, the effective amount is about 5 mg to about 33 mg per day. In embodiments, the effective amount is about 5 mg to about 32 mg per day. In embodiments, the effective amount is about 5 mg to about 31 mg per day. In embodiments, the effective amount is about 5 mg to about 30 mg per day. In embodiments, the effective amount is about 5 mg to about 29 mg per day. In embodiments, the effective amount is about 5 mg to about 28 mg per day. In embodiments, the effective amount is about 5 mg to about 27 mg per day. In embodiments, the effective amount is about 5 mg to about 26 mg per day. In embodiments, the effective amount is about 5 mg to about 25 mg per day. In embodiments, the lower amount in each of the ranges described herein is 6 mg. In embodiments, the lower amount in each of the ranges described herein is 7 mg. In embodiments, the lower amount in each of the ranges described herein is 8 mg. In embodiments, the lower amount in each of the ranges described herein is 9 mg.

[0149] In embodiments of the methods described herein, the effective amount of the glycerol compound is about 10 mg to about 100 mg per day. In embodiments, the effective amount is about 10 mg to about 99 mg per day. In embodiments, the effective amount is about 10 mg to about 98 mg per day. In embodiments, the effective amount is about 10 mg to about 97 mg per day. In embodiments, the effective amount is about 10 mg to about 96 mg per day. In embodiments, the effective amount is about 10 mg to about 95 mg per day. In embodiments, the effective amount is about 10 mg to about 94 mg per day. In embodiments, the effective amount is about 10 mg to about 93 mg per day. In embodiments, the effective amount is about 10 mg to about 92 mg per day. In embodiments, the effective amount is about 10 mg to about 91 mg per day. In embodiments, the effective amount is about 10 mg to about 90 mg per day. In embodiments, the effective amount is about 10 mg to about 89 mg per day. In embodiments, the effective amount is about 10 mg to about 88 mg per day. In embodiments, the effective amount is about 10 mg to about 87 mg per day. In embodiments, the effective amount is about 10 mg to about 86 mg per day. In embodiments, the effective amount is about 10 mg to about 85 mg per day. In embodiments, the effective amount is about 10 mg to about 84 mg per day. In embodiments, the effective amount is about 10 mg to about 83 mg per day. In embodiments, theeffective amount is about 10 mg to about 82 mg per day. In embodiments, the effective amount is about 10 mg to about 81 mg per day. In embodiments, the effective amount is about 10 mg to about 80 mg per day. In embodiments, the effective amount is about 10 mg to about 79 mg per day. In embodiments, the effective amount is about 10 mg to about 78 mg per day. In embodiments, the effective amount is about 10 mg to about 77 mg per day. In embodiments, the effective amount is about 10 mg to about 76 mg per day. In embodiments, the effective amount is about 10 mg to about 75 mg per day. In embodiments, the effective amount is about 10 mg to about 74 mg per day. In embodiments, the effective amount is about 10 mg to about 73 mg per day. In embodiments, the effective amount is about 10 mg to about 72 mg per day. In embodiments, the effective amount is about 10 mg to about 71 mg per day. In embodiments, the effective amount is about 10 mg to about 70 mg per day. In embodiments, the effective amount is about 10 mg to about 69 mg per day. In embodiments, the effective amount is about 10 mg to about 68 mg per day. In embodiments, the effective amount is about 10 mg to about 67 mg per day. In embodiments, the effective amount is about 10 mg to about 66 mg per day. In embodiments, the effective amount is about 10 mg to about 65 mg per day. In embodiments, the effective amount is about 10 mg to about 64 mg per day. In embodiments, the effective amount is about 10 mg to about 63 mg per day. In embodiments, the effective amount is about 10 mg to about 62 mg per day. In embodiments, the effective amount is about 10 mg to about 61 mg per day. In embodiments, the effective amount is about 10 mg to about 60 mg per day. In embodiments, the effective amount is about 10 mg to about 59 mg per day. In embodiments, the effective amount is about 10 mg to about 58 mg per day. In embodiments, the effective amount is about 10 mg to about 57 mg per day. In embodiments, the effective amount is about 10 mg to about 56 mg per day. In embodiments, the effective amount is about 10 mg to about 55 mg per day. In embodiments, the effective amount is about 10 mg to about 54 mg per day. In embodiments, the effective amount is about 10 mg to about 53 mg per day. In embodiments, the effective amount is about 10 mg to about 52 mg per day. In embodiments, the effective amount is about 10 mg to about 51 mg per day. In embodiments, the effective amount is about 10 mg to about 50 mg per day. In embodiments, the effective amount is about 10 mg to about 49 mg per day. In embodiments, the effective amount is about 10 mg to about 48 mg per day. In embodiments, the effective amount is about 10 mg to about 47 mg per day. In embodiments, the effective amount is about 10 mg to about 46 mg per day. In embodiments, the effective amount is about 10 mg to about 45 mg per day. In embodiments, the effective amount is about 10 mg to about 44 mg per day. In embodiments, the effective amount is about 10 mg to about 43 mg per day. In embodiments, the effective amount is about 10 mg to about 42 mg per day. Inembodiments, the effective amount is about 10 mg to about 41 mg per day. In embodiments, the effective amount is about 10 mg to about 40 mg per day. In embodiments, the effective amount is about 10 mg to about 39 mg per day. In embodiments, the effective amount is about 10 mg to about 38 mg per day. In embodiments, the effective amount is about 10 mg to about 37 mg per day. In embodiments, the effective amount is about 10 mg to about 36 mg per day. In embodiments, the effective amount is about 10 mg to about 35 mg per day. In embodiments, the effective amount is about 10 mg to about 34 mg per day. In embodiments, the effective amount is about 10 mg to about 33 mg per day. In embodiments, the effective amount is about 10 mg to about 32 mg per day. In embodiments, the effective amount is about 10 mg to about 31 mg per day. In embodiments, the effective amount is about 10 mg to about 30 mg per day. In embodiments, the effective amount is about 10 mg to about 29 mg per day. In embodiments, the effective amount is about 10 mg to about 28 mg per day. In embodiments, the effective amount is about 10 mg to about 27 mg per day. In embodiments, the effective amount is about 10 mg to about 26 mg per day. In embodiments, the effective amount is about 10 mg to about 25 mg per day. In embodiments, the lower amount in each of the ranges described herein is about 11 mg. In embodiments, the lower amount in each of the ranges described herein is about 12 mg. In embodiments, the lower amount in each of the ranges described herein is about 13 mg. In embodiments, the lower amount in each of the ranges described herein is about 14 mg. In embodiments, the lower amount in each of the ranges described herein is about 15 mg. In embodiments, the lower amount in each of the ranges described herein is about 16 mg. In embodiments, the lower amount in each of the ranges described herein is about 17 mg. In embodiments, the lower amount in each of the ranges described herein is about 18 mg. In embodiments, the lower amount in each of the ranges described herein is about 19 mg. In embodiments, the lower amount in each of the ranges described herein is about 20 mg. In embodiments, the lower amount in each of the ranges described herein is about 21 mg. In embodiments, the lower amount in each of the ranges described herein is about 22 mg. In embodiments, the lower amount in each of the ranges described herein is about 23 mg. In embodiments, the lower amount in each of the ranges described herein is about 24 mg. In embodiments, the lower amount in each of the ranges described herein is about 25 mg. In embodiments, the lower amount in each of the ranges described herein is about 26 mg. In embodiments, the lower amount in each of the ranges described herein is about 27 mg. In embodiments, the lower amount in each of the ranges described herein is about 28 mg. In embodiments, the lower amount in each of the ranges described herein is about 29 mg. In embodiments, the lower amount in each of the ranges described herein is about 30 mg.

[0150] In embodiments, the effective amount of the glycerol compound is 1 mg per day. In embodiments, the effective amount is 2 mg per day. In embodiments, the effective amount is 3 mg per day. In embodiments, the effective amount is 4 mg per day. In embodiments, the effective amount is 5 mg per day. In embodiments, the effective amount is 6 mg per day. In embodiments, the effective amount is 7 mg per day. In embodiments, the effective amount is 8 mg per day. In embodiments, the effective amount is 9 mg per day. In embodiments, the effective amount is 10 mg per day. In embodiments, the effective amount is 11 mg per day. In embodiments, the effective amount is 12 mg per day. In embodiments, the effective amount is 13 mg per day. In embodiments, the effective amount is 14 mg per day. In embodiments, the effective amount is 15 mg per day. In embodiments, the effective amount is 16 mg per day. In embodiments, the effective amount is 17 mg per day. In embodiments, the effective amount is 18 mg per day. In embodiments, the effective amount is 19 mg per day. In embodiments, the effective amount is 20 mg per day. In embodiments, the effective amount is 21 mg per day. In embodiments, the effective amount is 22 mg per day. In embodiments, the effective amount is 23 mg per day. In embodiments, the effective amount is 24 mg per day. In embodiments, the effective amount is 25 mg per day. In embodiments, the effective amount is 26 mg per day. In embodiments, the effective amount is 27 mg per day. In embodiments, the effective amount is 28 mg per day. In embodiments, the effective amount is 29 mg per day. In embodiments, the effective amount is 30 mg per day. In embodiments, the effective amount is 31 mg per day. In embodiments, the effective amount is 32 mg per day. In embodiments, the effective amount is 33 mg per day. In embodiments, the effective amount is 34 mg per day. In embodiments, the effective amount is 35 mg per day. In embodiments, the effective amount is 36 mg per day. In embodiments, the effective amount is 37 mg per day. In embodiments, the effective amount is 38 mg per day. In embodiments, the effective amount is 39 mg per day. In embodiments, the effective amount is 40 mg per day. In embodiments, the effective amount is 41 mg per day. In embodiments, the effective amount is 42 mg per day. In embodiments, the effective amount is 43 mg per day. In embodiments, the effective amount is 44 mg per day. In embodiments, the effective amount is 45 mg per day. In embodiments, the effective amount is 46 mg per day. In embodiments, the effective amount is 47 mg per day. In embodiments, the effective amount is 48 mg per day. In embodiments, the effective amount is 49 mg per day. In embodiments, the effective amount is 50 mg per day. In embodiments, the effective amount is 51 mg per day. In embodiments, the effective amount is 52 mg per day. In embodiments, the effective amount is 53 mg per day. In embodiments, the effective amount is 54 mg per day. In embodiments, the effective amount is 55 mg per day. In embodiments, the effective amount is 56 mg per day. Inembodiments, the effective amount is 57 mg per day. In embodiments, the effective amount is 58 mg per day. In embodiments, the effective amount is 59 mg per day. In embodiments, the effective amount is 60 mg per day. In embodiments, the effective amount is 61 mg per day. In embodiments, the effective amount is 62 mg per day. In embodiments, the effective amount is 63 mg per day. In embodiments, the effective amount is 64 mg per day. In embodiments, the effective amount is 65 mg per day. In embodiments, the effective amount is 66 mg per day. In embodiments, the effective amount is 67 mg per day. In embodiments, the effective amount is 68 mg per day. In embodiments, the effective amount is 69 mg per day. In embodiments, the effective amount is 70 mg per day. In embodiments, the effective amount is 71 mg per day. In embodiments, the effective amount is 72 mg per day. In embodiments, the effective amount is 73 mg per day. In embodiments, the effective amount is 74 mg per day. In embodiments, the effective amount is 75 mg per day. In embodiments, the effective amount is 76 mg per day. In embodiments, the effective amount is 77 mg per day. In embodiments, the effective amount is 78 mg per day. In embodiments, the effective amount is 79 mg per day. In embodiments, the effective amount is 80 mg per day. In embodiments, the effective amount is 81 mg per day. In embodiments, the effective amount is 82 mg per day. In embodiments, the effective amount is 83 mg per day. In embodiments, the effective amount is 84 mg per day. In embodiments, the effective amount is 85 mg per day. In embodiments, the effective amount is 86 mg per day. In embodiments, the effective amount is 87 mg per day. In embodiments, the effective amount is 88 mg per day. In embodiments, the effective amount is 89 mg per day. In embodiments, the effective amount is 91 mg per day. In embodiments, the effective amount is 92 mg per day. In embodiments, the effective amount is 93 mg per day. In embodiments, the effective amount is 94 mg per day. In embodiments, the effective amount is 95 mg per day. In embodiments, the effective amount is 96 mg per day. In embodiments, the effective amount is 97 mg per day. In embodiments, the effective amount is 98 mg per day. In embodiments, the effective amount is 99 mg per day. In embodiments, the effective amount is 90 mg per day. In embodiments, the effective amount is 100 mg per day. In embodiments, the effective amount is a range comprising any two of the aforementioned values herein (e.g., a range of about 25 mg to about 50 mg per day; a range of about 20 mg to about 30 mg per day; a range of about 18 mg to about 26 mg per day; and the like).

[0151] In embodiments of the methods described herein, the effective amount of the glycerol compound is about 0.1 mg / kg to about 10 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 9.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 9 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg toabout 8.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 8 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 7.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 7 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 6.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 6 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 5.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 4.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 4 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 3.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 3 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 2.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 2 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 1.5 mg / kg per day. In embodiments, the effective amount is about 0.1 mg / kg to about 1 mg / kg per day. In embodiments, the lower amount of each of the ranges described herein is 0.2 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 0.3 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 0.4 mg / kg.

[0152] In embodiments of the methods described herein, the effective amount of the glycerol compound is about 0.5 mg / kg to about 10 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 9.5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 9 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 8.5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 8 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 7.5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 7 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 6.5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 6 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 5.5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 4.5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 4 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 3.5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 3 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 2.5 mg / kg per day. Inembodiments, the effective amount is about 0.5 mg / kg to about 2 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 1.5 mg / kg per day. In embodiments, the effective amount is about 0.5 mg / kg to about 1 mg / kg per day. In embodiments, the lower amount of each of the ranges described herein is 0.6 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 0.7 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 0.8 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 0.9 mg / kg.

[0153] In embodiments of the methods described herein, the effective amount of the glycerol compound is about 1 mg / kg to about 10 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 9.5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 9 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 8.5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 8 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 7.5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 7 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 6.5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 6 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 5.5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 4.5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 4 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 3.5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 3 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 2.5 mg / kg per day. In embodiments, the effective amount is about 1 mg / kg to about 2 mg / kg per day. In embodiments, the lower amount of each of the ranges described herein is 1.1 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 1.2 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 1.3 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 1.4 mg / kg. In embodiments, the lower amount of each of the ranges described herein is 1.5 mg / kg.

[0154] In embodiments, of the methods described herein, the effective amount is administered once per day, twice per day, or three times per day. In embodiments, the effective amount is administered once per day. In embodiments, the effective amount is administered in a divided dose twice per day (e.g., if the effective amount is 50 mg per day, then 25 mg is administered twice per day). In embodiments, the effective amount is administered in a divided dose three times per day (e.g., if the effective amount is 66 mg per day, then 22 mg is administered threetimes per day).

[0155] Pharmaceutical Compositions

[0156] Provided herein are pharmaceutical compositions comprising a glycerol compound and a pharmaceutically acceptable excipient. In embodiments, the glycerol compound is a compound described herein or a pharmaceutically acceptable salt thereof (including embodiments thereof as described herein). In embodiments, the glycerol compound is a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is a pharmaceutically acceptable salt of a compound described herein (including embodiments thereof as described herein). In embodiments, the glycerol compound is glycerol, a glycerol acetate, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, glycerol-3-phosphate, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol, a glycerol acetate, or a combination thereof. In embodiments, the glycerol compound is glycerol, glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof. In embodiments, the glycerol compound is glycerol. In embodiments, the glycerol compound is glycerol acetate. In embodiments, the glycerol compound is glycerol monoacetin. In embodiments, the glycerol compound is glycerol diacetin. In embodiments, the glycerol compound is glycerol triacetin. In embodiments, the glycerol compound is glycerol-3-phosphate. In embodiments, the glycerol-3-phosphate further comprises a phosphate protecting group. In embodiments, the phosphate protecting group is pivaloyloxymethyl, S'-acyl-2-thioethyl, 4-acyloxybenzyl. isopropyloxycarbonyloxymethyl, phosphoramidate, or cycloSal

[0157] “Pharmaceutically acceptable excipient” and “pharmaceutically acceptable carrier” refer to a substance that aids the administration of an active agent to and absorption by a subject and can be included in the compositions of the present invention without causing a significant adverse toxicological effect on the patient. Non limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline solutions, lactated Ringer’s, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions (such as Ringer’s solution), alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethyl cellulose, polyvinyl pyrrolidine, and colors, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and / or aromatic substances and the like that do not deleteriouslyreact with the compounds of the invention. One of skill in the art will recognize that other pharmaceutical excipients are useful for the glycerol compounds described herein.

[0158] In embodiments, the pharmaceutical composition comprises from about 1 mg to about 100 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 99 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 98 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 97 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 96 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 95 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 94 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 93 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 92 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 91 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 90 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 89 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 88 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 87 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 86 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 85 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 84 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 83 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 82 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 81 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 80 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 79 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 78 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 77 mg of the glycerol compound. In embodiments, thepharmaceutical composition comprises from about 1 mg to about 76 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 75 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 74 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 73 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 72 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 71 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 70 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 69 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 68 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 67 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 66 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 65 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 64 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 63 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 62 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 61 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 60 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 59 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 58 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 57 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 56 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 55 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 54 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 53 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 52 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg toabout 51 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 50 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 49 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 48 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 47 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 46 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 45 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 44 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 43 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 42 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 41 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 40 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 39 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 38 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 37 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 36 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 35 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 34 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 33 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 32 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 31 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 30 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 29 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 28 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 27 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 1 mg to about 26 mg of the glycerol compound. In embodiments, thepharmaceutical composition comprises from about 1 mg to about 25 mg of the glycerol compound. In embodiments, the lower amount in each of the ranges described herein is 2 mg. In embodiments, the lower amount in each of the ranges described herein is 3 mg. In embodiments, the lower amount in each of the ranges described herein is 4 mg.

[0159] In embodiments, the pharmaceutical composition comprises from about 5 mg to about 100 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 99 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 98 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 97 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 96 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 95 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 94 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 93 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 92 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 91 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 90 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 89 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 88 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 87 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 86 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 85 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 84 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 83 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 82 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 81 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 80 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 79 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg toabout 78 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 77 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 76 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 75 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 74 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 73 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 72 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 71 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 70 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 69 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 68 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 67 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 66 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 65 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 64 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 63 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 62 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 61 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 60 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 59 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 58 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 57 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 56 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 55 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 54 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 53 mg of the glycerol compound. In embodiments, thepharmaceutical composition comprises from about 5 mg to about 52 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 51 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 50 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 49 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 48 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 47 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 46 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 45 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 44 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 43 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 42 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 41 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 40 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 39 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 38 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 37 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 36 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 35 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 34 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 33 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 32 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 31 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 30 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 29 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 28 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg toabout 27 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 26 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 5 mg to about 25 mg of the glycerol compound. In embodiments, the lower amount in each of the ranges described herein is 6 mg. In embodiments, the lower amount in each of the ranges described herein is 7 mg. In embodiments, the lower amount in each of the ranges described herein is 8 mg. In embodiments, the lower amount in each of the ranges described herein is 9 mg.

[0160] In embodiments, the pharmaceutical composition comprises from about 10 mg to about 100 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 99 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 98 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 97 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 96 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 95 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 94 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 93 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 92 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 91 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 90 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 89 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 88 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 87 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 86 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 85 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 84 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 83 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 82 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 81 mg of the glycerol compound. In embodiments, thepharmaceutical composition comprises from about 10 mg to about 80 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 79 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 78 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 77 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 76 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 75 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 74 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 73 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 72 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 71 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 70 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 69 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 68 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 67 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 66 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 65 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 64 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 63 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 62 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 61 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 60 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 59 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 58 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 57 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 56 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg toabout 55 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 54 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 53 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 52 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 51 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 50 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 49 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 48 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 47 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 46 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 45 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 44 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 43 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 42 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 41 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 40 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 39 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 38 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 37 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 36 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 35 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 34 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 33 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 32 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 31 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 30 mg of the glycerol compound. In embodiments, thepharmaceutical composition comprises from about 10 mg to about 29 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 28 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 27 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 26 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises from about 10 mg to about 25 mg of the glycerol compound. In embodiments, the lower amount in each of the ranges described herein is about 11 mg. In embodiments, the lower amount in each of the ranges described herein is about 12 mg. In embodiments, the lower amount in each of the ranges described herein is about 13 mg. In embodiments, the lower amount in each of the ranges described herein is about 14 mg. In embodiments, the lower amount in each of the ranges described herein is about 15 mg. In embodiments, the lower amount in each of the ranges described herein is about 16 mg. In embodiments, the lower amount in each of the ranges described herein is about 17 mg. In embodiments, the lower amount in each of the ranges described herein is about 18 mg. In embodiments, the lower amount in each of the ranges described herein is about 19 mg. In embodiments, the lower amount in each of the ranges described herein is about 20 mg. In embodiments, the lower amount in each of the ranges described herein is about 21 mg. In embodiments, the lower amount in each of the ranges described herein is about 22 mg. In embodiments, the lower amount in each of the ranges described herein is about 23 mg. In embodiments, the lower amount in each of the ranges described herein is about 24 mg. In embodiments, the lower amount in each of the ranges described herein is about 25 mg. In embodiments, the lower amount in each of the ranges described herein is about 26 mg. In embodiments, the lower amount in each of the ranges described herein is about 27 mg. In embodiments, the lower amount in each of the ranges described herein is about 28 mg. In embodiments, the lower amount in each of the ranges described herein is about 29 mg. In embodiments, the lower amount in each of the ranges described herein is about 30 mg.

[0161] In embodiments, the pharmaceutical composition comprises about 1 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 2 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 3 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 4 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 5 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 6 mg of the glycerol compound. In embodiments, the pharmaceutical compositioncomprises about 7 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 8 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 9 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 10 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 11 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 12 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 13 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 14 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 15 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 16 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 17 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 18 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 19 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 20 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 21 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 22 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 23 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 24 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 25 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 26 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 27 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 28 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 29 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 30 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 31 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 32 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 33 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 34 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 35 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 36 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 37 mg of the glycerol compound. Inembodiments, the pharmaceutical composition comprises about 38 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 39 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 40 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 41 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 42 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 43 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 44 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 45 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 46 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 47 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 48 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 49 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 50 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 51 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 52 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 53 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 54 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 55 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 56 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 57 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 58 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 59 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 60 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 61 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 62 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 63 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 64 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 65 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 66 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 67 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 68mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 69 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 70 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 71 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 72 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 73 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 74 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 75 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 76 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 77 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 78 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 79 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 80 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 81 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 82 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 83 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 84 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 85 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 86 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 87 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 88 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 89 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 91 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 92 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 93 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 94 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 95 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 96 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 97 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 98 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 99 mg of the glycerol compound. In embodiments, thepharmaceutical composition comprises about 90 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises about 100 mg of the glycerol compound. In embodiments, the pharmaceutical composition comprises a range comprising any two of the aforementioned values herein (e.g., a range of about 25 mg of the glycerol compound to about 50 mg of the glycerol compound; a range of about 20 mg of the glycerol compound to about 30 mg of the glycerol compound; a range of about 18 mg of the glycerol compound to about 26 mg of the glycerol compound; and the like).

[0162] The pharmaceutical compositions may be in a form suitable for oral use, for example, as tablets, capsules, troches, lozenges, gums, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups, solutions, microbeads or elixirs.Pharmaceutical compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions, and such compositions may contain one or more agents such as, for example, sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets, capsules and the like contain the active ingredient in admixture with nontoxic pharmaceutically acceptable excipients that are suitable for the manufacture thereof.These excipients may be, for example, diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, com starch, or alginic acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc. In embodiments, the pharmaceutical compositions provided herein are in form of a tablet, pill, capsule, dragee, lotion, cream, patch, gummy, solution, or suspension. In embodiments, the pharmaceutical compositions provided herein are suitable for oral, parenteral, topical, intradermal, or intramuscular administration.

[0163] The tablets, capsules and the like suitable for oral administration may be uncoated or coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action. For example, a time-delay material such as glyceryl monostearate or glyceryl distearate may be employed. They may also be coated by techniques known in the art to form osmotic therapeutic tablets for controlled release. Additional agents include biodegradable or biocompatible particles or a polymeric substance such as polyesters, polyamine acids, hydrogel, polyvinyl pyrrolidone, polyanhydrides, polyglycolic acid, ethylenevinylacetate, methylcellulose, carboxymethylcellulose, protamine sulfate, or lactide / glycolide copolymers, polylactide / glycolide copolymers, or ethylenevinylacetate copolymers in order to control delivery of an administered composition. For example, the oral agent can be entrapped inmicrocapsules prepared by coacervation techniques or by interfacial polymerization, by the use of hydroxymethylcellulose or gelatin-microcapsules or poly(methylmethacrolate) microcapsules, respectively, or in a colloid drug delivery system. Colloidal dispersion systems include macromolecule complexes, nano-capsules, microspheres, microbeads, and lipid-based systems, including oil-in-water emulsions, micelles, mixed micelles, and liposomes. Methods for the preparation of the above-mentioned formulations will be apparent to those skilled in the art.

[0164] Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate, kaolin or microcrystalline cellulose, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin, or olive oil.

[0165] In embodiments, the pharmaceutical composition is for oral administration. In embodiments, the pharmaceutical composition is an orally administrable solid. In embodiments, the pharmaceutical composition is a tablet, a capsule, a powder, a lozenge, or a granule. In embodiments, the pharmaceutical composition is a tablet, a capsule, a powder, or a granule. In embodiments, the pharmaceutical composition is a tablet, a capsule, or a powder. In embodiments, the pharmaceutical composition is a tablet or a capsule. In embodiments, the pharmaceutical composition is a tablet. In embodiments, the pharmaceutical composition is a capsule. In embodiments, the pharmaceutical composition is a powder. In embodiments, the pharmaceutical composition is a granule. In embodiments, the pharmaceutical composition is a lozenge.

[0166] Aqueous suspensions contain the active materials in admixture with excipients suitable for the manufacture thereof. Such excipients can be suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinyl-pyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents, for example a naturally-occurring phosphatide (e.g., lecithin), or condensation products of an alkylene oxide with fatty acids (e.g., polyoxy-ethylene stearate), or condensation products of ethylene oxide with long chain aliphatic alcohols (e.g., for heptadecaethyleneoxycetanol), or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol (e.g., polyoxyethylene sorbitol monooleate), or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides (e.g., polyethylene sorbitan monooleate). The aqueous suspensions may also contain one or more preservatives.

[0167] Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquidparaffin. The oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents, such as those set forth above, and flavoring agents may be added to provide a palatable oral preparation.

[0168] Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, and optionally one or more suspending agents and / or preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified herein.

[0169] The pharmaceutical compositions of the present disclosure may also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example, liquid paraffin, or mixtures of these. Suitable emulsifying agents may be naturally occurring gums, for example, gum acacia or gum tragacanth; naturally occurring phosphatides, for example, soy bean, lecithin, and esters or partial esters derived from fatty acids; hexitol anhydrides, for example, sorbitan monooleate; and condensation products of partial esters with ethylene oxide, for example, polyoxyethylene sorbitan monooleate.

[0170] In embodiments, the pharmaceutical composition is for oral administration. In embodiments, the pharmaceutical composition is an orally administrable liquid. In embodiments, the orally administrable liquid is a solution or a suspension. In embodiments, the orally administrable liquid is a solution. In embodiments, the orally administrable liquid is a suspension. In embodiments, the suspension is an emulsion.

[0171] After a pharmaceutical composition has been formulated, it may be stored in sterile vials as a solution, suspension, gel, emulsion, solid, or dehydrated or lyophilized powder. Such formulations may be stored either in a ready -to-use form, a lyophilized form requiring reconstitution prior to use, a liquid form requiring dilution prior to use, or other acceptable form. In some embodiments, the pharmaceutical composition is provided in a single-use container (e.g., a single-use vial, ampule, syringe, or autoinjector, whereas a multi-use container (e.g., a multi-use vial) is provided in other embodiments.

[0172] Formulations can also include carriers to protect the composition against rapid degradation or elimination from the body, such as a controlled release formulation, including liposomes, hydrogels, prodrugs and microencapsulated delivery systems. For example, a timedelay material such as glyceryl monostearate or glyceryl stearate alone, or in combination with a wax, may be employed. Any drug delivery apparatus may be used to deliver the compounds described herein, including implants (e.g., implantable pumps) and catheter systems, slow injection pumps and devices, all of which are well known to the skilled artisan.

[0173] Depot injections, which are generally administered subcutaneously or intramuscularly.may also be utilized to release a compound disclosed herein over a defined period of time. Depot injections are usually either solid- or oil-based and generally comprise at least one of the formulation components set forth herein. One of ordinary skill in the art is familiar with possible formulations and uses of depot injections.

[0174] The pharmaceutical compositions may be in the form of a sterile injectable aqueous or oleagenous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents mentioned herein. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example, as a solution in 1,3-butane diol.Acceptable diluents, solvents and dispersion media that may be employed include water, Ringer's solution, isotonic sodium chloride solution, Cremophor® EL (BASF, Parsippany, NJ) or phosphate buffered saline (PBS), ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), and suitable mixtures thereof. In addition, sterile fixed oils are conventionally employed as a solvent or suspending medium; for this purpose, any bland fixed oil may be employed, including synthetic mono- or diglycerides. Moreover, fatty acids, such as oleic acid, find use in the preparation of injectables. Prolonged absorption of particular injectable formulations can be achieved by including an agent that delays absorption (e.g., aluminum monostearate or gelatin).

[0175] The singular forms “a,” "an." and “the” include plural referents unless the context clearly dictates otherwise. It should further be understood that The term “a” entity or “an” entity refers to one or more of that entity. For example, a nucleic acid molecule refers to one or more nucleic acid molecules. As such, the terms “a”, “an”, “one or more” and “at least one” can be used interchangeably. Similarly, the terms “comprising”, “including” and “having” can be used interchangeably.

[0176] The term “about” means a range of values including the specified value, which a person of ordinary skill in the art would consider reasonably similar to the specified value. In embodiments, about means within a standard deviation using measurements generally acceptable in the art. In embodiments, about means a range extending to + / - 10% of the specified value. In embodiments, about means the specified value.

[0177] Throughout the application alternatives are written in Markush groups, for example, each amino acid position that contains more than one possible amino acid. It is specifically contemplated that each member of the Markush group should be considered separately, thereby comprising another embodiment, and the Markush group is not to be read as a single unit.

[0178] Embodiments Al to A24.

[0179] Embodiment Al. A compound of Formula (VIII) or a pharmaceutically acceptable salt thereof:Owherein RAand RBare each independently a substituted or unsubstituted alk l group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; RDand RFare each independently substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and L1. L2, L3, and L4are each independently substituted or unsubstituted alkylene

[0180] Embodiment A2. The compound of Embodiment Al, wherein RAand RBare each independently a substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety,, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; RDand REare each independently substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety.

[0181] Embodiment A3. The compound of Embodiment Al or A2, wherein the compound of formula (VIII) is a compound of Formula (VIIA):wherein RAand RBare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and RDand REare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety.

[0182] Embodiment A4. The compound of Embodiments Al to A3, wherein RAand RBare each independently unsubstituted Ci-is alkyl group or N-acetyl galactosamine moiety.

[0183] Embodiment A5. The compound of any one of Embodiments Al to A4, wherein RDand REare each independently a fibrate moiety or a statin moiety7.

[0184] Embodiment A6. The compound of any one of Embodiments Al to A5, wherein the fibrate moiety is a moiety selected from the group consisting of bezafibrate, ciprofi brale, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, and simifibrate moiety.

[0185] Embodiment A7. The compound of any one of Embodiments Al to A6, wherein the statin moiety is a moiety selected from the group consisting of atorvastatin. fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.

[0186] Embodiment A8. The compound of any one of Embodiments Al to A7, wherein (a) RAand RBare methyl, and RDandREare a fenofibrate moiety7; (b) RAand RBare ethyl, and RDand REare a fenofibrate moiety; (c) RAand RBare tert-butyl, and RDandREare a fenofibrate moiety; (d) RAand RBare CsHn, and RDandREare a fenofibrate moiety; (e) RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L3is -OCH2CH2-, and RDandREare a fenofibrate moiety7; (f) RAand RBare methyl, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety; (g) RAand RBare ethyl, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety; (h) RAand RBare tert-butyl, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety; (i) RAand RBare CsHn, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety; (j) RAand RBare N-acetyl galactosamine moiety. L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety; (k) RAand RBare methyl, and Rc, and RDare an acetyl rosuvastatin moiety; (1) RAand RBare ethyl, and RDand REare an acetyl rosuvastatin moiety; (m) RAand RBare tert-butyl, and RDand REare an acetyl rosuvastatin moiety7; (n) RAand RBare CsHn, and RDandREare an acetyl rosuvastatin moiety; (0) RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and RDand REare an acetyl rosuvastatin moiety; (p) RA, RB, RD, and REare methyl; (q) RAand RBare ethyl, and Ruand REare methyl; (r) RAand RBare tert-butyl, and RDandREare methyl; (s) RAand RBare CsHi?, and RDandREare methyl; or (t) RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L3is -OCH2CH2-. and RDandREare methyl.

[0187] Embodiment A9. A compound of Formula (VII) or a pharmaceutically acceptable salt thereof:owherein RAand RBare each independently a substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; L1and L2are each independently substituted or unsubstituted alkylene; Rcis independently hydrogen, halogen, substituted or unsubstituted alkyl, or acetoxy vinyl: n is 0, 1, 2. 3, or 4.

[0188] Embodiment A10. The compound of Embodiment A9, wherein RAand RBare each independently a substituted or unsubstituted Ci-24 al ky 1 group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; Rcis independently hydrogen, halogen, substituted or unsubstituted C1-24 alkyl group, or acetoxy vinyl; and L1and L2are each independently substituted or unsubstituted C1-24 alkyl group.

[0189] Embodiment All, The compound of Embodiment A9 or A10, wherein the compound of formula (VII) is a compound of Formula (VIIA):owherein RAand RBare each independently unsubstituted C1-24 alkyl group. N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; RCis independently hydrogen, halogen, unsubstituted C1-6alkyl, or acetoxyvinyl; and n is 0, 1, or 2.

[0190] Embodiment A12. The compound of any one of Embodiments A9 to Al 1, wherein RAand RBare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety

[0191] Embodiment A13. The compound of Embodiment A12, wherein RAand RBare each independently unsubstituted Ci-is alkyl group or N-acetyl galactosamine moiety.

[0192] Embodiment A14. The compound of any one of Embodiments A9 to A13, wherein: (a) RAand RBare methyl, Rcis 5-Br, and n is 1; (b) RAand RBare methyl. Rcis 5-CH3. and n is I; (c) RAand RBare methyl, Rcis 3, 5 -tert-butyl, and n is 2; (d) RAand RBare methyl, Rcis 5-(l -acetoxy vinyl), and n is 1; (e) RAand RBare ethyl, Rcis 5-Br, and n is I; (f) RAand RBare ethyl, Rcis 5-CH3, and n is 1; (g) RAand RBare ethyl, Rcis 3,5-tert-butyl, and n is 2; (h) RAand RBare ethyl, Rcis 5-(l -acetoxy vinyl), and n is 1; (i) RAand RBare n-butyl and n is 0; (j) RAand RBare n-butyl, Rcis 5-Br, and n is 1; (k) RAand RBare n-butyl, Rcis 5-CHs, and n is 1; (1) RAand RBare n-butyl, Rcis 3, 5 -tert- butyl, and n is 2; (m) RAand RBare n-butyl, Rcis 5-(l-acetoxyvinyl), and n is 1; (n) RAand RBare -CsHn and n is 0; (o) RAand RBare -CsHn, Rcis 5-Br, and n is 1; (p) RAand RBare -CsHn, Rcis 5-CHs, and n is 1; (q) RAand RBare -CsHn, Rcis 3,5-tert-butyl, and n is 2; (r) RAand RBare -CsHn, Rcis 5-(l-acetoxyvinyl), and n is 1; (s) RAand RBare N-acetyl-galactosamine moiety’, L1and L2are -CH2-, R100, R101. and R102are -C(O)CHy and L5is -OCH2CH2-, and n is 0; (t) RAand RBare N-acetyl galactosamine moiety, Rcis 5-Br, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 1; (u) RAand RBare N-acetyl galactosamine moiety', Rcis 5-CH3, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-. and n is 1; (v) RAand RBN-acetyl galactosamine moiety, Rcis 3,5-tert-butyl, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH₃, and L5is -OCH2CH2-, and n is 2; or (w) RAand RBare N-acetyl galactosamine moiety7, Rcis 5-(l -acetoxy vinyl), L1and L2are -CH2-, R100, R101, and R102are -C(O)CH₃, and L5is -OCH2CH2-, and n is 1.

[0193] Embodiment Al 5. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:R1O-p^°Rtf ' o T oR40R3 (I)wherein R1is hydrogen, a butyrate, a fibrate moiety, or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety, or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen.

[0194] Embodiment Al 6. A compound of Formula (II) or a pharmaceutically acceptable salt thereof:wherein R1, R2, R3, and R4are each independently hydrogen, acetate, propionate, butyrate, blacetyl galactosamine, N-acetyl galactosamine moiety7, a fibrate moiety, or a statin moiety; and L1, L2, L3, and L4are each independently hydrogen or substituted or unsubstituted alkylene.

[0195] Embodiment A 17. A compound of Formula (IV) or a pharmaceutically acceptable salt thereof:L3R3O OL4R40' 'O^^B(OH)2 (IV)wherein R3and R4are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine moiety, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety; and L3and L4are each independently hydrogen or substituted or unsubstituted alkylene.

[0196] Embodiment Al 8. A compound of Formula (V) or a pharmaceutically acceptable salt thereof:L2QOR-|R7OR2(V)wherein R1and R2are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety: provided that R1and R2are not simultaneously hydrogen: L1and L2are each independently hydrogen or substituted or unsubstituted alkylene; and R6and R7are independently hydrogen, unsubstituted Ci-6 alkyl, -Cl, -F, -Br, -I, or acetoxyvinyl.

[0197] Embodiment Al 9. A compound of Formula (VI) or a pharmaceutically acceptable salt thereof:OR5OFbjOR2(VI) wherein R1and R2are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine. N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety: provided that R1and R2are not simultaneously hydrogen; R ' are each independently hydrogen or substitutedor unsubstituted alkyl; and L1and L2are each independently hydrogen or substituted or unsubstituted alkylene.

[0198] Embodiment A20. The compound of any one of Embodiments Al to Al 9, wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalk lene.

[0199] Embodiment A21. The compound of Embodiment A20. wherein R100, R101. and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, or unsubstituted C1-12 heteroalkylene.

[0200] Embodiment A22. A pharmaceutical composition comprising an effective amount of the compound of any one of Embodiments Al to A21 and a pharmaceutically acceptable excipient.

[0201] Embodiment A23. A method of reducing craving for sugar, reducing a craving for alcohol, treating a disease mediated by fibroblast grow th factor 21, or treating citrin deficiency in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of any one of Embodiments Al to A21 or the pharmaceutical composition of Embodiment A22.

[0202] Embodiment A24. The method of Embodiment A23, w herein the disease mediated by fibroblast growth factor 21 is a metabolic disease, diabetes, obesity, overweight, alcohol use disorder, an eating disorder, fatty liver disease, nonalcoholic steatohepatitis, hepatic encephalopathy, cirrhosis, dyslipidemia, hypercholesterolemia, or hypertriglyceridemia.

[0203] Embodiments 1 to 461.

[0204] Embodiment 1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:0R3 (I)wherein R1is hydrogen, a butyrate, a fibrate moiety, or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety’, or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

[0205] Embodiment 2. The compound of Embodiment 1, wherein R1is butyrate, a fibrate moiety, or a statin moiety; and R2is butyrate, a fibrate moiety, or a statin.

[0206] Embodiment 3. The compound of Embodiment 1, wherein R1is hydrogen, buty rate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R2is hydrogen, butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate. clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety'; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen.

[0207] Embodiment 4. The compound of Embodiment 1, wherein R1is butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R2is butyrate, bezafibrate, ciprofibrate. clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin.

[0208] Embodiment 5. The compound of Embodiment 1, wherein R1is hydrogen, butyrate, fenofibrate, or rosuvastatin moiety; R2is hydrogen, butyrate, fenofibrate, or rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moietv; and R4ishydrogen, acetate, propionate, buty rate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen.

[0209] Embodiment 6. The compound of Embodiment 1, wherein R1is butyrate, fenofibrate, or rosuvastatin moiety; R2is butyrate, fenofibrate, or rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety.

[0210] Embodiment 7. The compound of Embodiment 6, wherein R1is fenofibrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen.

[0211] Embodiment 8. The compound of Embodiment 6, wherein R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen.

[0212] Embodiment 9. The compound of Embodiment 6, wherein R1is fenofibrate; R2is fenofibrate; R3is N-acetyl galactosamine moiety; and R4is N-acetyl galactosamine moiety.

[0213] Embodiment 10. The compound of Embodiment 6, wherein R1is fenofibrate; R2is fenofibrate; R3is butyrate; and R4is butyrate.

[0214] Embodiment 11. The compound of Embodiment 6, wherein R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety.

[0215] Embodiment 12. The compound of Embodiment 6, wherein R1is butyrate; R2is butyrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety.

[0216] Embodiment 13. The compound of Embodiment 6, yvherein R1is butyrate; R2is butyrate; R3is butyrate; and R4is butyrate.

[0217] Embodiment 14. The compound of Embodiment 6, wherein R1is butyrate; R2is butyrate; R3is hydrogen; and R4is hydrogen.

[0218] Embodiment 15. The compound of Embodiment 6, yvherein R1is butyrate; R2is fenofibrate; R3is N-acetyl galactosamine moiety; and R4is hydrogen.

[0219] Embodiment 16. The compound of Embodiment 6, wherein R1is rosuvastatin moiety; R2is fenofibrate; R3is butyrate; and R4is N-acetyl galactosamine moiety.

[0220] Embodiment 17. A pharmaceutical composition comprising the compound of any one of Embodiments 1 to 16 and a pharmaceutically acceptable excipient.

[0221] Embodiment 18. A pharmaceutical composition comprising an effective amount of a glycerol compound and a pharmaceutically acceptable excipient.

[0222] Embodiment 19. The pharmaceutical composition of Embodiment 18, yvherein the glycerol compound is glycerol.

[0223] Embodiment 20. The pharmaceutical composition of Embodiment 18, wherein the glycerol compound is glycerol acetate.

[0224] Embodiment 21. The pharmaceutical composition of Embodiment 18, wherein the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof.

[0225] Embodiment 22. The pharmaceutical composition of Embodiment 18, wherein the glycerol compound is glycerol monoacetin.

[0226] Embodiment 23. The pharmaceutical composition of Embodiment 18, wherein the glycerol compound is glycerol diacetin.

[0227] Embodiment 24. The pharmaceutical composition of Embodiment 18, wherein the glycerol compound is glycerol triacetin.

[0228] Embodiment 25. The pharmaceutical composition of Embodiment 18, wherein the glycerol compound is glycerol-3-phosphate.

[0229] Embodiment 26. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 1 mg to about 100 mg of the compound.

[0230] Embodiment 27. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 1 mg to about 75 mg of the compound.

[0231] Embodiment 28. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 1 mg to about 50 mg of the compound.

[0232] Embodiment 29. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 5 mg to about 100 mg of the compound.

[0233] Embodiment 30. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 5 mg to about 75 mg of the compound.

[0234] Embodiment 31. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 5 mg to about 50 mg of the compound.

[0235] Embodiment 32. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 10 mg to about 100 mg of the compound.

[0236] Embodiment 33. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 10 mg to about 75 mg of the compound.

[0237] Embodiment 34. The pharmaceutical composition of any one of Embodiments 17 to 25, comprising from about 10 mg to about 50 mg of the compound.

[0238] Embodiment 35. The pharmaceutical composition of any one of Embodiments 17 to 34, wherein the pharmaceutical composition is orally administrable.

[0239] Embodiment 36. The pharmaceutical composition of any one of Embodiments 17 to 34, wherein the pharmaceutical composition is an orally administrable solid.

[0240] Embodiment 37. The pharmaceutical composition of Embodiment 36, wherein theorally administrable solid is a tablet, capsule, powder, lozenge, or granule.

[0241] Embodiment 38. The pharmaceutical composition of any one of Embodiments 17 to 34, wherein the pharmaceutical composition is orally administrable liquid.

[0242] Embodiment 39. The pharmaceutical composition of Embodiment 38, wherein the orally administrable liquid is a solution or a suspension.

[0243] Embodiment 40. A method of reducing craving for sugar in a subject in need thereof, the method comprising administering to the subject an effective amount of a glycerol compound.

[0244] Embodiment 41. A method of reducing craving for alcohol in a subject in need thereof, the method comprising administering to the subject an effective amount of a glycerol compound.

[0245] Embodiment 42. A method of treating a disease mediated by fibroblast growth factor 21, the method comprising administering to the subject an effective amount of a glycerol compound.

[0246] Embodiment 43. The method of Embodiment 42, wherein the disease mediated by fibroblast growth factor 21 is a metabolic disease.

[0247] Embodiment 44. The method of Embodiment 42 or 43, wherein the disease is diabetes.

[0248] Embodiment 45. The method of Embodiment 42 or 43, wherein the disease is obesity.

[0249] Embodiment 46. The method of Embodiment 42 or 43, wherein the disease is overweight.

[0250] Embodiment 47. The method of Embodiment 42 or 43, wherein the disease is alcohol use disorder.

[0251] Embodiment 48. The method of Embodiment 42 or 43, wherein the disease is an eating disorder.

[0252] Embodiment 49. The method of Embodiment 48, wherein the eating disorder is anorexia nervosa.

[0253] Embodiment 50. The method of Embodiment 48, wherein the eating disorder is bulimia nervosa.

[0254] Embodiment 51. The method of Embodiment 48, wherein the eating disorder is bingeeating disorder.

[0255] Embodiment 52. The method of Embodiment 48, wherein the eating disorder is avoidant restrictive food intake disorder.

[0256] Embodiment 53. The method of Embodiment 48, wherein the eating disorder is pica, rumination disorder, or night eating syndrome.

[0257] Embodiment 54. The method of Embodiment 48, wherein the eating disorder is orthorexia.

[0258] Embodiment 55. The method of Embodiment 42 or 43, wherein the disease is fatty liver disease.

[0259] Embodiment 56. The method of Embodiment 42 or 43, wherein the disease is nonalcoholic steatohepatitis.

[0260] Embodiment 57. The method of Embodiment 42 or 43, wherein the disease is hepatic encephalopathy.

[0261] Embodiment 58. The method of Embodiment 42 or 43, wherein the disease is cirrhosis.

[0262] Embodiment 59. The method of Embodiment 42 or 43, wherein the disease is dyslipidemia.

[0263] Embodiment 60. The method of Embodiment 42 or 43, wherein the disease is hypercholesterolemia.

[0264] Embodiment 61. The method of Embodiment 42 or 43, wherein the disease is hypertriglyceridemia.

[0265] Embodiment 62. A method of treating citrin deficiency in a subject in need thereof, the method comprising administering to the subject an effective amount of a glycerol compound.

[0266] Embodiment 63. The method of any one of Embodiments 40 to 62, wherein the glycerol compound is a compound of Formula (I) or a pharmaceutically acceptable salt thereof:wherein R1is hydrogen, butyrate, a fibrate moiety, or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety, or a statin moiety7; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety7; provided that R1, R2, R3, and R4are not simultaneously hydrogen; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -0-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

[0267] Embodiment 64. The method of Embodiment 63, wherein R1is but rate, a fibrate moiety, or a statin moiety; and R2is butyrate, a fibrate moiety, or a statin.

[0268] Embodiment 65. The method of Embodiment 63, wherein R1is hydrogen, butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R2is hydrogen, butyrate, bezafibrate, ciprofibrate. clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin. fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen.

[0269] Embodiment 66. The method of Embodiment 63, wherein R1is butyrate, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin moiety; R2is butyrate, bezafibrate, ciprofibrate. clinofibrate, clofibrate, clofibride. fenofibrate, gemfibrozil, nafenopin, ronifibrate, simifibrate, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin.

[0270] Embodiment 67. The method of Embodiment 63, wherein R1is hydrogen, butyrate, fenofibrate, or rosuvastatin moiety; R2is hydrogen, butyrate, fenofibrate, or rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen.

[0271] Embodiment 68. The method of Embodiment 63, wherein R1is butyrate, fenofibrate, or rosuvastatin moiety; R2is butyrate, fenofibrate. or rosuvastatin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety.

[0272] Embodiment 69. The method of Embodiment 68, wherein R1is fenofibrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen.

[0273] Embodiment 70. The method of Embodiment 68, wherein R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen.

[0274] Embodiment 71. The method of Embodiment 68, wherein R1is fenofibrate; R2is fenofibrate; R3is N-acetyl galactosamine moiety; and R4is N-acetyl galactosamine moiety.

[0275] Embodiment 72. The method of Embodiment 68, wherein R1is fenofibrate; R2isfenofibrate; R3is buty rate; and R4is buty rate.

[0276] Embodiment 73. The method of Embodiment 68, wherein R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety.

[0277] Embodiment 74. The method of Embodiment 68, wherein R1is butyrate; R2is but rate; R3is hydrogen; and R4is N-acetyl galactosamine moiety7.

[0278] Embodiment 75. The method of Embodiment 68, wherein R1is butyrate; R2is butyrate; R3is butyrate; and R4is butyrate.

[0279] Embodiment 76. The method of Embodiment 68, wherein R1is butyrate; R2is butyrate; R3is hydrogen; and R4is hydrogen.

[0280] Embodiment 77. The method of Embodiment 68, wherein R1is butyrate; R2is fenofibrate; R3is N-acetyl galactosamine moiety; and R4is hydrogen.

[0281] Embodiment 78. The method of Embodiment 68, wherein R1is rosuvastatin moiety; R2is fenofibrate; R3is butyrate; and R4is N-acetyl galactosamine moiety.

[0282] Embodiment 79. The method of any one of Embodiments 40 to 62, wherein the glycerol compound is glycerol.

[0283] Embodiment 80. The method of any one of Embodiments 40 to 62, wherein the glycerol compound is glycerol acetate.

[0284] Embodiment 81. The method of any one of Embodiments 40 to 62, wherein the glycerol compound is glycerol monoacetin, glycerol diacetin, glycerol triacetin, or a combination of two or more thereof.

[0285] Embodiment 82. The method of any one of Embodiments 40 to 62, wherein the glycerol compound is glycerol monoacetin.

[0286] Embodiment 83. The method of any one of Embodiments 40 to 62, wherein the glycerol compound is glycerol diacetin.

[0287] Embodiment 84. The method of any one of Embodiments 40 to 62, wherein the glycerol compound is glycerol triacetin.

[0288] Embodiment 85. The method of any one of Embodiments 40 to 62, wherein the glycerol compound is glycerol-3-phosphate.

[0289] Embodiment 86. The method of Embodiment 85, wherein the glycerol-3-phosphate further comprises a phosphate protecting group.

[0290] Embodiment 87. The method of Embodiment 86, wherein the phosphate protecting group is pivaloyloxymethyl, isopropyloxy carbonyloxymethyl, S-acyl-2-thioethyl, 4-acyloxybenzyl. phosphoramidate, or cycloSal.

[0291] Embodiment 88. The method of any one of Embodiments 40 to 87, wherein theeffective amount is from about 1 mg to about 100 mg.

[0292] Embodiment 89. The method of any one of Embodiments 40 to 87, wherein the effective amount is from about 1 mg to about 75 mg of the compound.

[0293] Embodiment 90. The method of any one of Embodiments 40 to 87, wherein the effective amount is from about 1 mg to about 50 mg of the compound.

[0294] Embodiment 91. The method of any one of Embodiments 40 to 87, wherein the effective amount is from about 5 mg to about 100 mg of the compound.

[0295] Embodiment 92. The method of any one of Embodiments 40 to 87, wherein the effective amount is from about 5 mg to about 75 mg of the compound.

[0296] Embodiment 93. The method of any one of Embodiments 40 to 87, wherein the effective amount is from about 5 mg to about 50 mg of the compound.

[0297] Embodiment 94. The method of any one of Embodiments 40 to 87, wherein the effective amount is from about 10 mg to about 100 mg of the compound.

[0298] Embodiment 95. The method of any one of Embodiments 40 to 87, wherein the effective amount is from about 10 mg to about 75 mg of the compound.

[0299] Embodiment 96. The method of any one of Embodiments 40 to 87, wherein the effective amount is from about 10 mg to about 50 mg of the compound.

[0300] Embodiment 97. The method of any one of Embodiments 40 to 87, wherein the effective amount is about 0.1 mg / kg to about 10 mg / kg per day.

[0301] Embodiment 98. The method of any one of Embodiments 40 to 87, wherein the effective amount is about 0.1 mg / kg to about 5 mg / kg per day.

[0302] Embodiment 99. The method of any one of Embodiments 40 to 87, wherein the effective amount is about 0.5 mg / kg to about 4 mg / kg per day.

[0303] Embodiment 100. The method of any one of Embodiments 40 to 87, wherein the effective amount is about 0.5 mg / kg to about 3 mg / kg per day.

[0304] Embodiment 101. The method of any one of Embodiments 40 to 87, wherein the effective amount is about 0.5 mg / kg to about 2 mg / kg per day.

[0305] Embodiment 102. The method of any one of Embodiments 40 to 101, comprising orally administering the effective amount of the glycerol compound to the subject.

[0306] Embodiment 103. The method of any one of Embodiments 40 to 102, further comprising administering to the subject an effective amount of leptin or leptin analog.

[0307] Embodiment 104. The method of any one of Embodiments 40 to 102, further comprising administering to the subject an effective amount of metreleptin.

[0308] Embodiment 105. The method of any one of Embodiments 40 to 104, furthercomprising administering to the subject an effective amount of lactate, alpha-hydroxybutyrate. acetaldehyde, reduced nicotinamide adenine dinucleotide, malate, glucose, xylulose, xylulose-5-phosphate, fructose, fructose-2,6-bisphosphate, or a combination of two or more thereof.

[0309] Embodiment 106. A compound of Formula (II) or a pharmaceutically acceptable salt thereof:I 3 R3O Owherein R1, R2, R3, and R4are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety’; and L1, L2, L3, and L4are each independently hydrogen or substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

[0310] Embodiment 107. The compound of Embodiment 106, wherein R1, R2, R3, and R4are not simultaneously hydrogen

[0311] Embodiment 108. The compound of Embodiment 106, wherein R1is hydrogen, a buty rate, a fibrate moiety', or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety, or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen.

[0312] Embodiment 109. The compound of any one of Embodiments 106 to 108, w herein L1,L2, L3, and L4are each independently unsubstituted alkyd ene.

[0313] Embodiment 110. The compound of any one of Embodiments 106 to 108, wherein L1, L2, L3, and L4are each independently unsubstituted Ci-6 alkylene.

[0314] Embodiment 111. The compound of any' one of Embodiments 106 to 108, wherein L1and L2are methylene and L3and L4are ethylene.

[0315] Embodiment 112. The compound of any one of Embodiments 106 to 111, wherein R1and R2are acetate and R3and R4are each independently a fibrate moiety or a statin moiety.

[0316] Embodiment 113. The compound of Embodiment 3, wherein R1and R2are acetate, R3and R4are each independently a fibrate or a statin moiety, L1and L2are methylene, and L3and L4are ethylene.

[0317] Embodiment 114. The compound of any one of Embodiments 106 to 111, wherein at least one of R1, R2, R3, and R4is a fibrate moiety or a statin moiety.

[0318] Embodiment 115. The compound of any' one of Embodiments 106 to 111, wherein one of R1, R2, R3, and R4is a fibrate moiety' or a statin moiety7.

[0319] Embodiment 116. The compound of any one of Embodiments 106 to 111, wherein at least two of R1, R2. R3. and R4is a fibrate moiety or a statin moiety.

[0320] Embodiment 117. The compound of any one of Embodiments 106 to 111, wherein two of R1, R2, R3, and R4are a fibrate moiety' or a statin moiety'.

[0321] Embodiment 118. The compound of any one of Embodiments 106 to 111, wherein at least three of R1, R2, R3, and R4are a fibrate moiety or a statin moiety.

[0322] Embodiment 119. The compound of any one of Embodiments 106 to 111, wherein three of R1, R2, R3, and R4are a fibrate moiety or a statin moiety.

[0323] Embodiment 120. The compound of any one of Embodiments 106 to 111, wherein R1, R2, R3, and R4are a fibrate moiety or a statin moiety7.

[0324] Embodiment 121. The compound of any one of Embodiments 106 to 111, wherein at least one of R1, R2, R3, and R4is a fibrate moiety.

[0325] Embodiment 122. The compound of any one of Embodiments 106 to 111, wherein one of R1, R2, R3. and R4is a fibrate moiety.

[0326] Embodiment 123. The compound of any one of Embodiments 106 to 111, wherein at least two of R1, R2, R3, and R4are a fibrate moiety7.

[0327] Embodiment 124. The compound of any one of Embodiments 106 to 111, wherein two of R1, R2, R3, and R4are a fibrate moiety7.

[0328] Embodiment 125. The compound of any one of Embodiments 106 to 111, wherein at least three of R1, R2, R3, and R4are a fibrate moiety.

[0329] Embodiment 126. The compound of any one of Embodiments 106 to 111, wherein three of R1, R2. R3, and R4are a fibrate moiety.

[0330] Embodiment 127. The compound of any one of Embodiments 106 to 111, wherein R1, R2, R3, and R4are a fibrate moiety.

[0331] Embodiment 128. The compound of any one of Embodiments 106 to 111, wherein at least one of R1. R2, R3, and R4is a statin.

[0332] Embodiment 129. The compound of any one of Embodiments 106 to 111, wherein one of R1, R2, R3, and R4is a statin.

[0333] Embodiment 130. The compound of any one of Embodiments 106 to 111, wherein at least two of R1, R2, R3, and R4are a statin.

[0334] Embodiment 131. The compound of any one of Embodiments 106 to 111, wherein two of R1, R2, R3, and R4are a statin.

[0335] Embodiment 132. The compound of any7one of Embodiments 106 to 111, wherein at least three of R1, R2, R3, and R4are a statin.

[0336] Embodiment 133. The compound of any one of Embodiments 106 to 111, wherein three of R1, R2. R3. and R4are a statin.

[0337] Embodiment 134. The compound of any one of Embodiments 106 to 111, wherein R1, R2, R3, and R4are a statin.

[0338] Embodiment 135. A compound of Formula (IV) or a pharmaceutically acceptable salt thereof:L3R3O' OB(OH)2 (iv)wherein R3and R4are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine moiety, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety; and L3and L4are each independently hydrogen or substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety' has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

[0339] Embodiment 136. The compound of Embodiment 135, wherein that R3and R4are not simultaneously hydrogen

[0340] Embodiment 137. The compound of Embodiment 135, wherein R1is hydrogen, a butyrate, a fibrate moiety, or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety, or a statin moiety7; R3is hydrogen, acetate, propionate, butyrate. orN-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, buty rate, or N-acetyl galactosamine moiety7; provided that R1. R2. R3. and R4are not simultaneously hydrogen.

[0341] Embodiment 138. The compound of any one of Embodiments 135 to 137, wherein L3and L4are each independently7unsubstituted alkylene.

[0342] Embodiment 139. The compound of any one of Embodiments 135 to 137, wherein L3and L4are each independently unsubstituted Ci-6 alkylene.

[0343] Embodiment 140. The compound of any one of Embodiments 135 to 137, wherein L3and L4are ethylene.

[0344] Embodiment 141. The compound of Embodiment 135, wherein R3and R4are each independently a fibrate or a statin moiety7, and L3and L4are ethylene.

[0345] Embodiment 142. The compound of any one of Embodiments 135 to 140, wherein at least one of R3and R4is a fibrate moiety7or a statin moiety.

[0346] Embodiment 143. The compound of any one of Embodiments 135 to 140, wherein one of R3and R4is a fibrate moiety7or a statin moiety.

[0347] Embodiment 144. The compound of any one of Embodiments 135 to 140, wherein R3and R4are each independently a fibrate moiety.

[0348] Embodiment 145. The compound of any7one of Embodiments 135 to 140, wherein at least one of R3and R4is a fibrate moiety7.

[0349] Embodiment 146. The compound of any one of Embodiments 135 to 140, wherein one of R3and R4is a fibrate moiety.

[0350] Embodiment 147. The compound of any one of Embodiments 135 to 140, wherein R3and R4are each independently a fibrate moiety.

[0351] Embodiment 148. The compound of any one of Embodiments 135 to 140, wherein at least one of R3and R4is a statin.

[0352] Embodiment 149. The compound of any one of Embodiments 135 to 140, wherein one of R3and R4is a statin.

[0353] Embodiment 150. The compound of any one of Embodiments 135 to 140, wherein R3and R4are each independently a statin.

[0354] Embodiment 151. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety.

[0355] Embodiment 152. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is bezafibrate moiety.

[0356] Embodiment 153. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is ciprofibrate moiety.

[0357] Embodiment 154. The compound of any one of Embodiments 106-127. 135-143. and 144-147, wherein the fibrate is clinofibrate moiety.

[0358] Embodiment 155. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is clofibrate moiety.

[0359] Embodiment 156. The compound of any one of Embodiments 106-127. 135-143. and 144-147, wherein the fibrate is clofibride.

[0360] Embodiment 157. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is fenofibrate moiety.

[0361] Embodiment 158. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is gemfibrozil.

[0362] Embodiment 159. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is nafenopin.

[0363] Embodiment 160. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is ronifibrate moiety.

[0364] Embodiment 161. The compound of any one of Embodiments 106-127, 135-143, and 144-147, wherein the fibrate is simifibrate moiety.

[0365] Embodiment 162. The compound of any one of Embodiments 106-120, 128-134, and 148-150, wherein the statin is atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin.

[0366] Embodiment 163. The compound of any one of Embodiments 106-120, 128-134, and 148-150, wherein the statin is atorvastatin.

[0367] Embodiment 164. The compound of any one of Embodiments 106-120, 128-134, and 148-150, wherein the statin is fluvastatin.

[0368] Embodiment 165. The compound of any one of Embodiments 106-120, 128-134, and 148-150, wherein the statin is lovastatin.

[0369] Embodiment 166. The compound of any one of Embodiments 106-120. 128-134. and 148-150, wherein the statin is pitavastatin.

[0370] Embodiment 167. The compound of any one of Embodiments 106-120, 128-134, and 148-150, wherein the statin is pravastatin.

[0371] Embodiment 168. The compound of any one of Embodiments 106-120. 128-134, and 148-150, wherein the statin is rosuvastatin.

[0372] Embodiment 169. The compound of any one of Embodiments 106-120, 128-134, and 148-150, wherein the statin is simvastatin.

[0373] Embodiment 170. A compound of Formula (V) or a pharmaceutically acceptable salt thereof:wherein R1and R2are each independently hydrogen, acetate, propionate, but rate. N-acetyl galactosamine, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety: provided that R1and R2are not simultaneously hydrogen; L1and L2are each independently hydrogen or substituted or unsubstituted alkylene; and R6and R7are independently hydrogen, unsubstituted Ci-6 alkyl, -Cl, -F, -Br, -I, or acetoxyvinyl; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH3, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

[0374] Embodiment 171. The compound of Embodiment 170, wherein R1is hydrogen, a butyrate, a fibrate moiety, or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety, or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1. R2. R3. and R4are not simultaneously hydrogen.

[0375] Embodiment 172. The compound of Embodiment 170 or 171, wherein R1and R2are acetate.

[0376] Embodiment 173. The compound of any one of Embodiments 170 to 172, wherein L1and L2are each independently unsubstituted alkylene.

[0377] Embodiment 174. The compound of any one of Embodiments 170 to 172, wherein L1and L2are each independently unsubstituted Ci-6 alkylene.

[0378] Embodiment 175. The compound of any one of Embodiments 170 to 172, w herein L1and L2are methylene.

[0379] Embodiment 176. The compound of any one of Embodiments 170 to 175, wherein R6is -CL -F, -Br, or -I.

[0380] Embodiment 177. The compound of any one of Embodiments 170 to 175, wherein R6is -Br.

[0381] Embodiment 178. The compound of any one of Embodiments 170 to 175, wherein R6is hydrogen.

[0382] Embodiment 179. The compound of any one of Embodiments 170 to 175, wherein R6is unsubstituted Ci-6 alkyl.

[0383] Embodiment 180. The compound of any one of Embodiments 170 to 175, wherein R6is methyl.

[0384] Embodiment 181. The compound of any one of Embodiments 170 to 175, wherein R6is tert-butyl.

[0385] Embodiment 182. The compound of any one of Embodiments 170 to 175, wherein R6is acetoxyvinyl.

[0386] Embodiment 183. The compound of any one of Embodiments 170 to 182, wherein R7is hydrogen.

[0387] Embodiment 184. The compound of any one of Embodiments 170 to 182, wherein R7is unsubstituted Ci-6 alkyl.

[0388] Embodiment 185. The compound of any one of Embodiments 170 to 182, wherein R7is tert-butyl.

[0389] Embodiment 186. The compound of Embodiment 170, wherein R1and R2are acetate, L1and L2are methylene, and R6is -Br.

[0390] Embodiment 187. The compound of Embodiment 170, wherein R1and R2are acetate, L1and L2are methylene, and R6is hydrogen.

[0391] Embodiment 188. The compound of Embodiment 170, wherein R1and R2are acetate, L1and L2are methylene, and R6is methyl.

[0392] Embodiment 189. The compound of Embodiment 170, wherein R1and R2are acetate, L1and L2are methylene, and R6is acetoxyvinyl.

[0393] Embodiment 190. The compound of Embodiment 170, wherein R1and R2are acetate, L1and L2are methylene, and R6and R7are tert-butyl.

[0394] Embodiment 191. A compound of Formula (VI) or a pharmaceutically acceptable salt thereof:OR5wherein R1and R2are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine. N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety: provided that R1and R2are not simultaneously hydrogen; R3are each independently hydrogen or substituted or unsubstituted alkyl; and L1and L2are each independently hydrogen or substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

[0395] Embodiment 192. The compound of Embodiment 191, wherein R1is hydrogen, a butyrate, a fibrate moiety, or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety, or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen.

[0396] Embodiment 193. The compound of Embodiment 191 or 192, wherein R1and R2are acetate.

[0397] Embodiment 194. The compound of any one of Embodiments 191 to 193, wherein R5are each independently hydrogen or unsubstituted alkyl.

[0398] Embodiment 195. The compound of Embodiment 24 or 25, wherein R5are each independently unsubstituted Ci-6 alkyl.

[0399] Embodiment 196. The compound of any one of Embodiments 191 to 193, wherein R ' is methyl.

[0400] Embodiment 197. The compound of any one of Embodiments 191 to 196, wherein L1and L2are each independently unsubstituted alkylene.

[0401] Embodiment 198. The compound of any one of Embodiments 191 to 196, wherein L1and L2are each independently unsubstituted Ci-6 alkylene.

[0402] Embodiment 199. The compound of any one of Embodiments 191 to 196, wherein L1and L2are methylene.

[0403] Embodiment 200. The compound of Embodiment 191, wherein R1and R2are acetate R5is methyl. L1and L2are methylene.

[0404] Embodiment 201. A compound having the structure:OAc

[0405] Embodiment 202. A compound having the structure:vOH

[0406] Embodiment 203. A compound having the structure:OAc

[0407] Embodiment 204. A compound having the structure:or a pharmaceutically acceptable salt thereof, wherein R3and R4are independently a fibrate moiety or a statin moiety.

[0408] Embodiment 205. The compound of Embodiment 204, wherein at least one of R3and R4is a fibrate moiety7or a statin moiety7.

[0409] Embodiment 206. The compound of Embodiment 204, wherein one of R' and R4is a fibrate moiety or a statin moiety.

[0410] Embodiment 207. The compound of Embodiment 204, wherein R3and R4are each independently a fibrate moiety7.

[0411] Embodiment 208. The compound of Embodiment 204, wherein at least one of R3and R4is a fibrate moiety.

[0412] Embodiment 209. The compound of Embodiment 204, wherein one of R3and R4is a fibrate moiety.

[0413] Embodiment 210. The compound of Embodiment 204, wherein R3and R4are each independently a fibrate moiety.

[0414] Embodiment 211. The compound of Embodiment 204, wherein at least one of R3and R4is a statin.

[0415] Embodiment 212. The compound of Embodiment 204, wherein one of R3and R4is a statin.

[0416] Embodiment 213. The compound of Embodiment 204, wherein R3and R4are each independently a statin.

[0417] Embodiment 214. The compound of any one of Embodiments 204 to 210, wherein thefibrate is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety.

[0418] Embodiment 215. The compound of Embodiment 214, wherein the fibrate is bezafibrate moiety.

[0419] Embodiment 216. The compound of Embodiment 214, wherein the fibrate is ciprofibrate moiety.

[0420] Embodiment 217. The compound of Embodiment 214, wherein the fibrate is clinofibrate moiety.

[0421] Embodiment 218. The compound of Embodiment 214, wherein the fibrate is clofibrate moiety.

[0422] Embodiment 219. The compound of Embodiment 214, wherein the fibrate is clofibride.

[0423] Embodiment 220. The compound of Embodiment 214, wherein the fibrate is fenofibrate moiety.

[0424] Embodiment 221. The compound of Embodiment 214, wherein the fibrate is gemfibrozil.

[0425] Embodiment 222. The compound of Embodiment 214, wherein the fibrate is nafenopin.

[0426] Embodiment 223. The compound of Embodiment 214, wherein the fibrate is ronifibrate moiety.

[0427] Embodiment 224. The compound of Embodiment 214, wherein the fibrate is simifibrate moiety.

[0428] Embodiment 225. The compound of any one of Embodiments 204-206 and 211-213, wherein the statin is atorvastatin. fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin.

[0429] Embodiment 226. The compound of Embodiment 225, wherein the statin is atorvastatin.

[0430] Embodiment 227. The compound of Embodiment 225, wherein the statin is fluvastatin.

[0431] Embodiment 228. The compound of Embodiment 225, wherein the statin is lovastatin.

[0432] Embodiment 229. The compound of Embodiment 225, wherein the statin is pitavastatin.

[0433] Embodiment 230. The compound of Embodiment 225, wherein the statin is pravastatin.

[0434] Embodiment 231. The compound of Embodiment 225, wherein the statin is rosuvastatin.

[0435] Embodiment 232. The compound of Embodiment 225, wherein the statin is simvastatin.

[0436] Embodiment 233. A compound having the structure:B(OH)2(III)wherein R3and R4are each independently a fibrate moiety, or a statin.

[0437] Embodiment 234. The compound of Embodiment 223, wherein at least one of R3and R4is a fibrate moiety or a statin moiety.

[0438] Embodiment 235. The compound of Embodiment 223, wherein one of R3and R4is a fibrate moiety or a statin moiety.

[0439] Embodiment 236. The compound of Embodiment 223, wherein R3and R4are each independently a fibrate moiety7.

[0440] Embodiment 237. The compound of Embodiment 223, wherein at least one of R3and R4is a fibrate moiety.

[0441] Embodiment 238. The compound of Embodiment 223, wherein one of R3and R4is a fibrate moiety.

[0442] Embodiment 239. The compound of Embodiment 223, wherein R3and R4are each independently a fibrate moiety.

[0443] Embodiment 240. The compound of Embodiment 223, wherein at least one of R3and R4is a statin.

[0444] Embodiment 241. The compound of Embodiment 223, wherein one of R3and R4is a statin.

[0445] Embodiment 242. The compound of Embodiment 223, wherein R3and R4are each independently a statin.

[0446] Embodiment 243. The compound of any one of Embodiments 223-239, wherein the fibrate is bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, or simifibrate moiety.

[0447] Embodiment 244. The compound of Embodiment 243, wherein the fibrate is bezafibrate moiety.

[0448] Embodiment 245. The compound of Embodiment 243, wherein the fibrate isciprofibrate moiety.

[0449] Embodiment 246. The compound of Embodiment 243, wherein the fibrate is clinofibrate moiety.

[0450] Embodiment 247. The compound of Embodiment 243, wherein the fibrate is clofibrate moiety.

[0451] Embodiment 248. The compound of Embodiment 243, wherein the fibrate is clofibride.

[0452] Embodiment 249. The compound of Embodiment 243, wherein the fibrate is fenofibrate moiety.

[0453] Embodiment 250. The compound of Embodiment 243, wherein the fibrate is gemfibrozil.

[0454] Embodiment 251. The compound of Embodiment 243, wherein the fibrate is nafenopin.

[0455] Embodiment 252. The compound of Embodiment 243, wherein the fibrate is ronifibrate moiety7.

[0456] Embodiment 253. The compound of Embodiment 243, wherein the fibrate is simifibrate moiety.

[0457] Embodiment 254. The compound of any one of Embodiments 223-235 and 240-242, wherein the statin is atorvastatin. fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin.

[0458] Embodiment 255. The compound of Embodiment 254, wherein the statin is atorvastatin.

[0459] Embodiment 256. The compound of Embodiment 254, wherein the statin is fluvastatin.

[0460] Embodiment 257. The compound of Embodiment 254, wherein the statin is lovastatin.

[0461] Embodiment 258. The compound of Embodiment 254, wherein the statin is pitavastatin.

[0462] Embodiment 259. The compound of Embodiment 254, wherein the statin is pravastatin.

[0463] Embodiment 260. The compound of Embodiment 254, wherein the statin is rosuvastatin.

[0464] Embodiment 261. The compound of Embodiment 254, wherein the statin is simvastatin.

[0465] Embodiment 262. A compound having the structure:

[0466] Embodiment 263. A compound having the structure:

[0467] Embodiment 264. A compound having the structure:OAcBu OAc, where tBu is tert-butyl.

[0468] Embodiment 265. A compound having the structure:

[0469] Embodiment 266. A compound having the structure:

[0470] Embodiment 267. The compound of any one of Embodiments 1-16 and 106-266, wherein the compound is a free base.

[0471] Embodiment 268. The compound of any one of Embodiments 1-16 and 106-266, wherein the compound is a pharmaceutically acceptable salt.

[0472] Embodiment 269. A compound of Formula (VII) or a pharmaceutically acceptable salt thereofowherein RAand RBare each independently a substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; L1and L2are each independently substituted or unsubstituted alkylene; Rcis independently hydrogen, halogen, substituted or unsubstituted alkyl, or acetoxyvinyl; n is 0, 1, 2, 3, or 4, wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

[0473] Embodiment 270. The compound of any one of Embodiments 1-6, 9, 11, 12, 15-17, 63, 67, 68, 71, 73, 74, 77, 78, 88-111, 135-140, 170-185, 191-200, and 269, wherein R100, R101, and R102are each independently hydrogen or -C(O)CH3, and L5is a bond, -O-, or unsubstituted C1-12 heteroalkylene.

[0474] Embodiment 271. The compound of Embodiment 270, wherein R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-.

[0475] Embodiment 272. The compound of any one of Embodiments 269 to 271, wherein RAand RBare each independently a substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety'; Rcis independently hydrogen, halogen, substituted or unsubstituted C1-24 alkyl group, or acetoxy vinyl; and L1and L2are each independently substituted or unsubstituted C1-24 alkylenegroup.

[0476] Embodiment 273. The compound of Embodiment 272, wherein RAand RBare each independently substituted or unsubstituted C1-12 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; Rcis independently hydrogen, halogen, substituted or unsubstituted C1-12 alkyl group, or acetoxyvinyl and L1and L2are each independently substituted or unsubstituted C1-12 alkyl group.

[0477] Embodiment 274. The compound of Embodiment 273, wherein RAand RBare each independently substituted or unsubstituted C1-6 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; Rcis independently hydrogen, halogen, substituted or unsubstituted C1-6 alkyl group, or acetoxyvinyl; and L1and L2are each independently substituted or unsubstituted C1-6 alkyl group.

[0478] Embodiment 275. The compound of any one of Embodiments 269 to 271, wherein the compound of formula (VII) is a compound of Formula (VIIA):owherein RAand RBare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; RCis independently hydrogen, halogen, unsubstituted C1-6alkyl, or acetoxyvinyl; and n is 0, 1, or 2.

[0479] Embodiment 276. The compound of any one of Embodiments 269 to 275, wherein n is 0.

[0480] Embodiment 277. The compound of any one of Embodiments 269-275, wherein n is 1.

[0481] Embodiment 278. The compound of any' one of Embodiments 269-275, wherein n is 2.

[0482] Embodiment 279. The compound of any one of Embodiments 269-275, wherein n is 3.

[0483] Embodiment 280. The compound of any one of Embodiments 269-275, wherein n is 4.

[0484] Embodiment 281. The compound of any one of Embodiments 269 to 280, wherein the alkyl group for RA, RB, Rc, L1, L2, or two or more thereof, is unsubstituted.

[0485] Embodiment 282. The compound of any one of Embodiments 269 to 280, w herein the alkyl group for RA, RB, Rc, L1, and L2is unsubstituted.

[0486] Embodiment 283. The compound of any one of Embodiments 269 to 280, wherein RAand RBare each independently unsubstituted Ci-is alkyl group or N-acetyl galactosamine moiety.

[0487] Embodiment 284. The compound of Embodiment 283, wherein RAand RBare each independently unsubstituted C1-12 alkyl group or N-acetyl galactosamine moiety.

[0488] Embodiment 285. The compound of Embodiment 283, wherein RAand RBare each independently unsubstituted C1-6 alkyl group or N-acetyl galactosamine moiety.

[0489] Embodiment 286. The compound of Embodiment 283, wherein RAand RBare each independently unsubstituted Ci-4 alkyl group or N-acetyl galactosamine moiety.

[0490] Embodiment 287. The compound of Embodiment 283, wherein RAand RBare each independently unsubstituted C6-12 alkyl group or N-acetyl galactosamine moiety.

[0491] Embodiment 288. The compound of Embodiment 283, wherein RAand RBare each independently unsubstituted Cs-io alkyl group or N-acetyl galactosamine moiety,.

[0492] Embodiment 289. The compound of any one of Embodiments 269 to 280, wherein RAand RBare each independently unsubstituted C1-24 alkyl.

[0493] Embodiment 290. The compound of Embodiment 289, wherein RAand RBare each independently unsubstituted Ci-is alkyl group.

[0494] Embodiment 291. The compound of Embodiment 289, wherein RAand RBare each independently unsubstituted C1-12 alkyl group.

[0495] Embodiment 292. The compound of Embodiment 289, wherein RAand RBare each independently unsubstituted C1-6 alkyl group.

[0496] Embodiment 293. The compound of Embodiment 289, wherein RAand RBare each independently unsubstituted C1-4 alkyl group.

[0497] Embodiment 294. The compound of Embodiment 289, wherein RAand RBare each independently unsubstituted C6-24 alkyl group.

[0498] Embodiment 295. The compound of Embodiment 289, wherein RAand RBare each independently unsubstituted Ce-18 alkyl group.

[0499] Embodiment 296. The compound of Embodiment 289, wherein RAand RBare each independently unsubstituted C6-12 alkyl group.

[0500] Embodiment 297. The compound of Embodiment 289, wherein RAand RBare each independently unsubstituted Cs-io alkyl group.

[0501] Embodiment 298. The compound of any one of Embodiments 269 to 280, wherein RAand RBare each N-acetyl galactosamine moiety.

[0502] Embodiment 299. The compound of Embodiment 275, wherein RAand RBare methyl, and n is 0.

[0503] Embodiment 300. The compound of Embodiment 275, wherein RAand RBare methyl, Rcis 5-Br, and n is 1.

[0504] Embodiment 301. The compound of Embodiment 275, wherein RAand RBare methyl, Rcis 5-CH3, and n is 1.

[0505] Embodiment 302. The compound of Embodiment 275, wherein RAand RBare methyl, Rcis 3, 5 -tert-butyl, and n is 2.

[0506] Embodiment 303. The compound of Embodiment 275, wherein RAand RBare methyl, Rcis 5 -(1 -acetoxy vinyl), and n is 1.

[0507] Embodiment 304. The compound of Embodiment 275, wherein RAand RBare ethyl, and n is 0.

[0508] Embodiment 305. The compound of Embodiment 275, wherein RAand RBare ethyl, Rcis 5-Br, and n is 1.

[0509] Embodiment 306. The compound of Embodiment 275, wherein RAand RBare ethyl, Rcis 5-CH3, and n is 1.

[0510] Embodiment 307. The compound of Embodiment 275, wherein RAand RBare ethyl, Rcis 3, 5 -tert-butyl, and n is 2.

[0511] Embodiment 308. The compound of Embodiment 275, wherein RAand RBare ethyl, Rcis 5 -(1 -acetoxy vinyl), and n is 1.

[0512] Embodiment 309. The compound of Embodiment 275, wherein RAand RBare n-butyl and n is 0.

[0513] Embodiment 310. The compound of Embodiment 275, wherein RAand RBare n-butyl, Rcis 5-Br, and n is 1.

[0514] Embodiment 311. The compound of Embodiment 275, wherein RAand RBare n-butyl, Rcis 5-CH3, and n is 1.

[0515] Embodiment 312. The compound of Embodiment 275, wherein RAand RBare n-butyl, Rcis 3, 5 -tert-butyl, and n is 2.

[0516] Embodiment 313. The compound of Embodiment 275, wherein RAand RBare n-butyl, Rcis 5-(l -acetoxy vinyl), and n is 1.

[0517] Embodiment 314. The compound of Embodiment 275, wherein RAand RBare -CsHn and n is 0.

[0518] Embodiment 315. The compound of Embodiment 275, wherein RAand RBare -CsHn, Rcis 5-Br, and n is 1.

[0519] Embodiment 316. The compound of Embodiment 275, wherein RAand RBare -CsHu, Rcis 5-CH3, and n is 1.Ill

[0520] Embodiment 317. The compound of Embodiment 275, wherein RAand RBare -CsHn, Rcis 3,5-tert-butyl, and n is 2.

[0521] Embodiment 318. The compound of Embodiment 275, wherein RAand RBare -CsHn, Rcis 5 -(1 -acetoxy vinyl), and n is 1.

[0522] Embodiment 319. The compound of Embodiment 269, wherein RAand RBare N-acetyl-galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 0.

[0523] Embodiment 320. The compound of Embodiment 269, wherein RAand RBare N-acetyl galactosamine moiety, Rcis 5-Br, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 1.

[0524] Embodiment 321. The compound of Embodiment 269, wherein RAand RBare N-acetyl galactosamine moiety, Rcis 5-CH3, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L3is -OCH2CH2-, and n is 1.

[0525] Embodiment 322. The compound of Embodiment 269, wherein RAand RBN-acetyl galactosamine moiety, Rcis 3.5 -tert-butyl, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 2.

[0526] Embodiment 323. The compound of Embodiment 269, wherein RAand RBare N-acetyl galactosamine moiety. Rcis 5 -(1 -acetoxy vinyl), L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 1.

[0527] Embodiment 324. A compound of Formula (VIII) or a pharmaceutically acceptable salt thereof:owherein RAand RBare each independently a substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety', acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; RDand REare each independently substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and L1, L2, L3, and L4are each independently substituted or unsubstituted alkylene; wherein the N-acetylgalactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

[0528] Embodiment 325. The compound of Embodiment 324, wherein R100, R101, and R102are each independently hydrogen or -C(O)CH3, and L5is a bond, -O-, or unsubstituted C1-12 heteroalkylene.

[0529] Embodiment 326. The compound of Embodiment 324, wherein R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-.

[0530] Embodiment 327. The compound of any one of Embodiments 324 to 326, wherein RAand RBare each independently a substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; RDand REare each independently substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety.

[0531] Embodiment 328. The compound of Embodiment 327, wherein RDand REare each independently substituted or unsubstituted C1-12 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and L1, L2, L3, and L4are each independently substituted or unsubstituted C1-12 alkyl group.

[0532] Embodiment 329. The compound of Embodiment 327, wherein RDand REare each independently substituted or unsubstituted C1-6 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and L1, L2, L3, and L4are each independently substituted or unsubstituted C1-6 alkyl group.

[0533] Embodiment 330. The compound of any one of Embodiments 324 to 326, wherein the compound of formula (VIII) is a compound of Formula (VIIA):wherein RAand RBare each independently unsubstituted C1-24 alkyl group, N-acelyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and RDand REare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety.

[0534] Embodiment 331. The compound of any one of Embodiments 324 or 330, wherein RAand RBare each independently unsubstituted C1-18 alkyl group or N-acetyl galactosamine moiety.

[0535] Embodiment 332. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C1-12 alkyl group or N-acetyl galactosamine moiety.

[0536] Embodiment 333. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C1-6 alkyl group or N-acetyl galactosamine moiety.

[0537] Embodiment 334. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C1-4 alkyl group or N-acetyl galactosamine moiety.

[0538] Embodiment 335. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C6-24 alkyl group or N-acetyl galactosamine moiety.

[0539] Embodiment 336. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted Ce-18 alkyl group or N-acetyl galactosamine moiety.

[0540] Embodiment 337. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C6-12 alkyl group or N-acetyl galactosamine moiety.

[0541] Embodiment 338. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted Cs-io alkyl group or N-acetyl galactosamine moiety.

[0542] Embodiment 339. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C1-24 alkyl group.

[0543] Embodiment 340. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted Ci-18 alkyl group.

[0544] Embodiment 341. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C1-12 alkyl group.

[0545] Embodiment 342. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted Ci-6 alkyl group.

[0546] Embodiment 343. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted Ci-4 alkyl group.

[0547] Embodiment 344. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C6-24 alkyl group.

[0548] Embodiment 345. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted Ce-is alkyl group.

[0549] Embodiment 346. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted C6-12 alkyl group.

[0550] Embodiment 347. The compound of Embodiment 331, wherein RAand RBare each independently unsubstituted Cs-io alkyl group.

[0551] Embodiment 348. The compound of Embodiment 331, wherein RAand RBare each independently N-acetyl galactosamine moiety7.

[0552] Embodiment 349. The compound of any one of Embodiments 324 to 330, wherein RAis the alkyl group and RBis N-acetyl galactosamine moiety.

[0553] Embodiment 350. The compound of any one of Embodiments 324 to 330, wherein RBis the alkyl group, RAis N-acetyl galactosamine moiety7.

[0554] Embodiment 351. The compound of any one of Embodiments 324 to 350, wherein one of RDis a fibrate moiety or a statin moiety and REis substituted or unsubstituted alkyl group.

[0555] Embodiment 352. The compound of any one of Embodiments 324 to 350, wherein one of RDis a fibrate moiety and REis substituted or unsubstituted alkyl group.

[0556] Embodiment 353. The compound of any one of Embodiments 324 to 350, wherein one of RDis a statin moiety and REis substituted or unsubstituted alkyl group.

[0557] Embodiment 354. The compound of any one of Embodiments 324 to 350, wherein one of REis a fibrate moiety or a statin moietys and RDis substituted or unsubstituted alkyl group.

[0558] Embodiment 355. The compound of any one of Embodiments 324 to 350, wherein one of REis a fibrate moiety and RDis substituted or unsubstituted alkyl group.

[0559] Embodiment 356. The compound of any one of Embodiments 324 to 350, wherein one of REis a statin moiety and RDis substituted or unsubstituted alkyl group.

[0560] Embodiment 357. The compound of any one of Embodiments 324 to 350, wherein RDand REare each independently a fibrate moiety7.

[0561] Embodiment 358. The compound of any one of Embodiments 324 to 350, wherein RDand REare each independently a statin moiety.

[0562] Embodiment 359. The compound of any one of Embodiments 322 to 346, wherein RDis a fibrate moiety and REis a statin moiety.

[0563] Embodiment 360. The compound of any one of Embodiments 324 to 350, wherein REis a fibrate moiety and RDis a statin moiety.

[0564] Embodiment 361. The compound of any one of Embodiments 324 to 360, wherein the fibrate moiety is a moiety' selected from the group consisting of bezafibrate, ciprofibrate, clinofibrate, clofibrate. clofibride, fenofibrate. gemfibrozil, nafenopin, ronifibrate, and simifibrate moiety.

[0565] Embodiment 362. The compound of Embodiment 361, wherein the fibrate moiety is bezafibrate moiety.

[0566] Embodiment 363. The compound of Embodiment 361, wherein the fibrate moiety is ciprofibrate moiety.

[0567] Embodiment 364. The compound of Embodiment 361, wherein the fibrate moiety is clinofibrate moiety.

[0568] Embodiment 365. The compound of Embodiment 361, wherein the fibrate moiety is clofibrate moiety.

[0569] Embodiment 366. The compound of Embodiment 361, wherein the fibrate moiety is clofibride.

[0570] Embodiment 367. The compound of Embodiment 361, wherein the fibrate moiety is fenofibrate moiety.

[0571] Embodiment 368. The compound of Embodiment 361, wherein the fibrate moiety is gemfibrozil.

[0572] Embodiment 369. The compound of Embodiment 361, wherein the fibrate moiety is nafenopin.

[0573] Embodiment 370. The compound of Embodiment 361, wherein the fibrate moiety is ronifibrate moiety.

[0574] Embodiment 371. The compound of Embodiment 361, wherein the fibrate moiety is simifibrate moiety.

[0575] Embodiment 372. The compound of any one of Embodiments 324 to 371, wherein the statin moiety is a moiety selected from the group consisting of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.

[0576] Embodiment 373. The compound of Embodiment 372, wherein the statin moiety is atorvastatin.

[0577] Embodiment 374. The compound of Embodiment 372, wherein the statin moiety isfluvastatin.

[0578] Embodiment 375. The compound of Embodiment 372, wherein the statin moiety is lovastatin.

[0579] Embodiment 376. The compound of Embodiment 372, wherein the statin moiety is pitavastatin.

[0580] Embodiment 377. The compound of Embodiment 372, wherein the statin moiety is pravastatin.

[0581] Embodiment 378. The compound of Embodiment 372, wherein the statin moiety is rosuvastatin.

[0582] Embodiment 379. The compound of Embodiment 372, wherein the statin moiety is simvastatin.

[0583] Embodiment 380. The compound of any one of Embodiments 324 to 350, wherein RDand REare each independently unsubstituted C1-12 alkyl group.

[0584] Embodiment 381. The compound of Embodiment 380, wherein RDand REare each independently unsubstituted C1-6 alkyl group.

[0585] Embodiment 382. The compound of Embodiment 380, wherein RDand REare each independently unsubstituted methyl or unsubstituted ethyl.

[0586] Embodiment 383. The compound of Embodiment 330, wherein RA, RB, RD, andREare methyl.

[0587] Embodiment 384. The compound of Embodiment 330, wherein RAand RBare ethyl, and RDand REare methyl.

[0588] Embodiment 385. The compound of Embodiment 330, wherein RAand RBare tertbutyl, and RDandREare methyl.

[0589] Embodiment 386. The compound of Embodiment 330, wherein RAand RBare CsHn, and RDandREare methyl.

[0590] Embodiment 387. The compound of Embodiment 324, wherein RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and RDandREare methyl.

[0591] Embodiment 388. The compound of Embodiment 330, wherein RAand RBare methyl, and Rc, andRDare an acetyl rosuvastatin moiety.

[0592] Embodiment 389. The compound of Embodiment 330, wherein RAand RBare ethyl, and RDandREare an acety l rosuvastatin moiety.

[0593] Embodiment 390. The compound of Embodiment 330, wherein RAand RBare tertbutyl, and RDandREare an acetyl rosuvastatin moiety.

[0594] Embodiment 391. The compound of Embodiment 330, wherein RAand RBare CsHn, and RDandREare an acetyl rosuvastatin moiety.

[0595] Embodiment 392. The compound of Embodiment 324, wherein RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L3is -OCH2CH2-, and RDandREare an acetyl rosuvastatin moiety.

[0596] Embodiment 393. The compound of Embodiment 330, wherein RAand RBare methyl, and RDandREare a fenofibrate moiety.

[0597] Embodiment 394. The compound of Embodiment 330, wherein RAand RBare ethyl, and RDandREare a fenofibrate moiety.

[0598] Embodiment 395. The compound of Embodiment 330, wherein RAand RBare tertbutyl, and RDandREare a fenofibrate moiety.

[0599] Embodiment 396. The compound of Embodiment 330, wherein RAand RBare CsHn, and RDandREare a fenofibrate moiety.

[0600] Embodiment 397. The compound of Embodiment 324, wherein RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and RDandREare a fenofibrate moiety.

[0601] Embodiment 398. The compound of Embodiment 330, wherein RAand RBare methyl, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety.

[0602] Embodiment 399. The compound of Embodiment 330, wherein RAand RBare ethyl, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety.

[0603] Embodiment 400. The compound of Embodiment 330, wherein RAand RBare tertbutyl, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety.

[0604] Embodiment 401. The compound of Embodiment 330, wherein RAand RBare CsHn, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety.

[0605] Embodiment 402. The compound of Embodiment 324, wherein RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L3is -OCH2CH2-, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety.

[0606] Embodiment 403. A pharmaceutical composition comprising an effective amount of the compound of any one of Embodiments 1-16 and 106-402 and a pharmaceutically acceptable excipient.

[0607] Embodiment 404. The pharmaceutical composition of Embodiment 403, comprising from about 0.01 mg to about 1,000 mg of the compound.

[0608] Embodiment 405. The pharmaceutical composition of Embodiment 403, comprising from about 0.1 mg to about 500 mg of the compound.

[0609] Embodiment 406. The pharmaceutical composition of Embodiment 403, comprising from about 1 mg to about 250 mg of the compound.

[0610] Embodiment 407. The pharmaceutical composition of Embodiment 403, comprising from about 5 mg to about 200 mg of the compound.

[0611] Embodiment 408. The pharmaceutical composition of Embodiment 403, comprising from about 5 mg to about 100 mg of the compound.

[0612] Embodiment 409. The pharmaceutical composition of Embodiment 403, comprising from about 5 mg to about 50 mg of the compound.

[0613] Embodiment 410. The pharmaceutical composition of Embodiment 399, comprising from about 10 mg to about 100 mg of the compound.

[0614] Embodiment 411. The pharmaceutical composition of Embodiment 403, comprising from about 10 mg to about 75 mg of the compound.

[0615] Embodiment 412. The pharmaceutical composition of Embodiment 403, comprising from about 10 mg to about 50 mg of the compound.

[0616] Embodiment 413. The pharmaceutical composition of any one of Embodiments 378 to 399, wherein the pharmaceutical composition is orally administrable.

[0617] Embodiment 414. The pharmaceutical composition of Embodiment 409, wherein the pharmaceutical composition is an orally administrable solid.

[0618] Embodiment 415. The pharmaceutical composition of Embodiment 410, wherein the orally administrable solid is a tablet, capsule, powder, lozenge, or granule.

[0619] Embodiment 416. The pharmaceutical composition of Embodiment 409, wherein the pharmaceutical composition is orally administrable liquid.

[0620] Embodiment 417. The pharmaceutical composition of Embodiment 412, wherein the orally administrable liquid is a solution or a suspension.

[0621] Embodiment 418. A method of reducing craving for sugar in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of any one of Embodiments 1-16 and 106-402 or the pharmaceutical composition of any one of Embodiments 403 to 417.

[0622] Embodiment 419. A method of reducing craving for alcohol in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of any one of Embodiments 1-16 and 106-402 or the pharmaceutical composition of any one of Embodiments 403 to 417.

[0623] Embodiment 420. A method of treating a disease mediated by fibroblast growth factor 21, the method comprising administering to the subject an effective amount of the compound ofany one of Embodiments 1-16 and 106-402 or the pharmaceutical composition of any one of Embodiments 403 to 417.

[0624] Embodiment 421. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is a metabolic disease.

[0625] Embodiment 422. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is diabetes.

[0626] Embodiment 423. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is obesity.

[0627] Embodiment 424. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is overweight.

[0628] Embodiment 425. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is alcohol use disorder.

[0629] Embodiment 426. The method of Embodiment 420, w herein the disease mediated by fibroblast growth factor 21 an eating disorder.

[0630] Embodiment 427. The method of Embodiment 426, wherein the eating disorder is anorexia nervosa.

[0631] Embodiment 428. The method of Embodiment 426, w herein the eating disorder is bulimia nervosa.

[0632] Embodiment 429. The method of Embodiment 426, wherein the eating disorder is binge-eating disorder.

[0633] Embodiment 430. The method of Embodiment 426, w herein the eating disorder is avoidant restrictive food intake disorder.

[0634] Embodiment 431. The method of Embodiment 426, wherein the eating disorder is pica, rumination disorder, or night eating syndrome.

[0635] Embodiment 432. The method of Embodiment 426, wherein the eating disorder is orthorexia.

[0636] Embodiment 433. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is fatty liver disease.

[0637] Embodiment 434. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is nonalcoholic steatohepatitis.

[0638] Embodiment 435. The method of Embodiment 420, w herein the disease mediated by fibroblast growth factor 21 is hepatic encephalopathy.

[0639] Embodiment 436. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is cirrhosis.

[0640] Embodiment 437. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is dyslipidemia.

[0641] Embodiment 438. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is hypercholesterolemia.

[0642] Embodiment 439. The method of Embodiment 420, wherein the disease mediated by fibroblast growth factor 21 is hypertriglyceridemia.

[0643] Embodiment 440. A method of treating citrin deficiency in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of any one of Embodiments 1-16 and 106-402 or the pharmaceutical composition of any one of Embodiments 403 to 417.

[0644] Embodiment 441. The method of any one of Embodiments 418 to 440, wherein the effective amount is from about 0.001 mg to about 1,000 mg.

[0645] Embodiment 442. The method of Embodiment 441, wherein the effective amount is from about 0.01 mg to about 1,000 mg.

[0646] Embodiment 443. The method of Embodiment 441, wherein the effective amount is from about 0.1 mg to about 500 mg of the compound.

[0647] Embodiment 444. The method of Embodiment 441, wherein the effective amount is from about 1 mg to about 250 mg of the compound.

[0648] Embodiment 445. The method of Embodiment 441, wherein the effective amount is from about 5 mg to about 200 mg of the compound.

[0649] Embodiment 446. The method of Embodiment 441, wherein the effective amount is from about 5 mg to about 100 mg of the compound.

[0650] Embodiment 447. The method of Embodiment 441, wherein the effective amount is from about 5 mg to about 50 mg of the compound.

[0651] Embodiment 448. The method of Embodiment 441, wherein the effective amount is from about 10 mg to about 100 mg of the compound.

[0652] Embodiment 449. The method of Embodiment 441, wherein the effective amount is from about 10 mg to about 75 mg of the compound.

[0653] Embodiment 450. The method of Embodiment 441, wherein the effective amount is from about 10 mg to about 50 mg of the compound.

[0654] Embodiment 451. The method of any one of Embodiments 418 to 440, wherein the effective amount is about 0.001 mg / kg to about 250 mg / kg per day.

[0655] Embodiment 452. The method of Embodiment 451, wherein the effective amount is about 0.01 mg / kg to about 100 mg / kg per day.

[0656] Embodiment 453. The method of Embodiment 451, wherein the effective amount is about 0.1 mg / kg to about 100 mg / kg per day.

[0657] Embodiment 454. The method of Embodiment 451, wherein the effective amount is about 0.5 mg / kg to about 100 mg / kg per day.

[0658] Embodiment 455. The method of Embodiment 451, wherein the effective amount is about 0.5 mg / kg to about 50 mg / kg per day.

[0659] Embodiment 456. The method of Embodiment 451, wherein the effective amount is about 0.5 mg / kg to about 20 mg / kg per day.

[0660] Embodiment 457. The method of any one of Embodiments 418 to 456, comprising orally administering the effective amount of the compound to the subject.

[0661] Embodiment 458. The method of any one of Embodiments 418 to 457, further comprising administering to the subject an effective amount of leptin or leptin analog.

[0662] Embodiment 459. The method of any one of Embodiments 418 to 457, further comprising administering to the subject an effective amount of metreleptin.

[0663] Embodiment 460. The compound of any one of Embodiments 1-16 and 106-402, wherein the compound is capable of releasing in vivo glycerol-3-phosphate, acetate moiety, propionate moiety, butyrate moiety, N-acetyl galactosamine moiety, fibrate, statin, or a combination of two or more thereof.

[0664] Embodiment 461. The compound of any one of Embodiments 1-16 and 106-402, wherein the compound is capable of releasing in vitro glycerol-3-phosphate, acetate moiety, propionate moiety, butyrate moiety, N-acetyl galactosamine moiety, fibrate, statin, or a combination of two or more thereof.EXAMPLES

[0665] Example 1

[0666] It has been discovered herein that glycerol-3-phosphate is the ChREBP activator. Moreover, glycerol-3-phosphate is the metabolite that can explain activation of ChREBP in all the conditions considered to be paradoxical and that, of the metabolites that become elevated in models of citrin deficiency, glycerol-3-phosphate is the metabolite that activates ChREBP and leads to high level expression of FGF21.

[0667] Consistent with the prediction that glycerol is a precursor to the FGF21 inducer and that loss of the citrin gene sensitizes to the accumulation of the inducer, in FIG. 1, it has been shown that glycerol activates ChREBP in a mouse hepatocyte cell line that is deleted for the SLC25A13 gene causing high expression of FGF21.

[0668] In FIGS. 2A-2D, it has been shown that wild type C57BL / 6 mice treated with glycerolshow activation of ChREBP with induced expression of LPK and FGF21.

[0669] Example 2

[0670] A compound of Formula (1) will be prepared wherein R1is fenofibrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen. It will be shown that the compound can be delivered to hepatocytes. It will be shown that the compound can release glycerol-3-phosphate. It will be shown that the compound can release fenofibrate moiety. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of FGF21, lower cholesterol, reduce cravings for sweets and ethanol, and treat fatty liver disease.

[0671] Example 3

[0672] A compound of Formula (I) will be prepared wherein R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is hydrogen. It will be shown that the compound can be delivered to hepatocytes. It will be shown that the compound can release glycerol-3-phosphate. It will be shown that the compound can release fenofibrate moiety. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of FGF21, lower cholesterol, reduce cravings for sweets and ethanol, and treat fatty liver disease.

[0673] Example 4

[0674] A compound of Formula (I) will be prepared wherein R1is fenofibrate; R2is fenofibrate; R3is N-acetyl galactosamine moiety; and R4is N-acetyl galactosamine moiety. It will be shown that the compound can be delivered to hepatocytes. It will be shown that the compound can release glycerol-3-phosphate. It will be shown that the compound can release fenofibrate moiety. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of FGF21, lower cholesterol, reduce cravings for sweets and ethanol, and treat fatty liver disease.

[0675] Example 5

[0676] A compound of Formula (1) will be prepared wherein R1is fenofibrate; R2is fenofibrate; R3is butyrate; and R4is butyrate. It will be shown that the compound can be delivered to hepatocytes. It w ill be shown that the compound can release glycerol-3-phosphate. It will be shown that the compound can release fenofibrate moiety. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of FGF21, lower cholesterol, reduce cravings for sweets and ethanol, and treat fatty liver disease.

[0677] Example 6

[0678] A compound of Formula (I) will be prepared wherein R1is butyrate; R2is fenofibrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety. It will be shown that the compound can be delivered to hepatocytes. It will be shown that the compound can release glycerol-3-phosphate. It will be shown that the compound can release fenofibrate moiety. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of FGF21, lower cholesterol, reduce cravings for sweets and ethanol, and treat fatty liver disease.

[0679] Example 7

[0680] A compound of Formula (I) will be prepared wherein R1is butyrate; R2is butyrate; R3is hydrogen; and R4is N-acetyl galactosamine moiety. It will be shown that the compound can be delivered to hepatocytes. It will be shown that the compound can release glycerol-3-phosphate. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of FGF21, lower cholesterol, reduce cravings for sweets and ethanol, and treat fatty liver disease.

[0681] Example 8

[0682] A compound of Formula (I) will be prepared wherein R1is butyrate; R2is butyrate; R3is butyrate; and R4is butyrate. It will be shown that the compound can be delivered to hepatocytes. It will be shown that the compound can release glycerol-3-phosphate. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of FGF21, lower cholesterol, reduce cravings for sweets and ethanol, and treat fatty liver disease.

[0683] Example 9

[0684] A compound of Formula (I) will be prepared wherein R1is butyrate; R2is butyrate; R3is hydrogen; and R4is hydrogen. It will be shown that the compound can be delivered to hepatocytes. It will be shown that the compound can release glycerol-3-phosphate. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of FGF21, lower cholesterol, reduce cravings for sweets and ethanol, and treat fatty liver disease.

[0685] Example 10

[0686] A compound of Formula (I) will be prepared wherein R1is butyrate; R2is fenofibrate; R3is N-acetyl galactosamine moiety; and R4is hydrogen. It will be shown that the compound can be delivered to hepatocytes. It will be shown that the compound can release glycerol-3-phosphate. It will be shown that the compound can release fenofibrate moiety. The compound will also be tested for its ability to activate ChREBP, PPARalpha, induce expression of ...

Claims

CLAIMSWhat is claimed is:

1. A compound of Formula (VIII) or a pharmaceutically acceptable salt thereof:owherein RAand RBare each independently a substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; RDand REare each independently substituted or unsubstituted alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and L1, L2, L3, and L4are each independently substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH3, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

2. The compound of claim 1, wherein R100, R101, and R102are each independently hydrogen or -C(O)CH3, and L5is a bond, -O-, or unsubstituted C1-12 heteroalkylene.

3. The compound of claim 1, wherein RAand RBare each independently a substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety,, acetate, propionate, butyrate, a fibrate moiety7, or a statin moiety; RDand REare each independently substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate,propionate, butyrate, a fibrate moiety, or a statin moiety.

4. The compound of claim 1, wherein the compound of formula (VIII) is a compound of Formula (VIIA):wherein RAand RBare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; and RDand REare each independently unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety. acetate, propionate, butyrate, a fibrate moiety, or a statin moiety.

5. The compound of claim 1, wherein RAand RBare each independently unsubstituted Ci-is alkyl group or N-acetyl galactosamine moiety.

6. The compound of claim 1, wherein RDand RFare each independently a fibrate moiety or a statin moiety.

7. The compound of claim 1, wherein the fibrate moiety is a moiety selected from the group consisting of bezafibrate, ciprofibrate. clinofibrate, clofibrate, clofibride, fenofibrate, gemfibrozil, nafenopin, ronifibrate, and simifibrate moiety; and wherein the statin moiety is a moiety selected from the group consisting of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.

8. The compound of claim 1, wherein(a) RAand RBare methyl, and RDand REare a fenofibrate moiety;(b) RAand RBare ethyl, and RDand RFare a fenofibrate moiety;(c) RAand RBare tert-butyl, and RDand REare a fenofibrate moiety;(d) RAand RBare CsHn, and RDand REare a fenofibrate moiety;(e) RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and RDandREare a fenofibrate moiety;(f) RAand RBare methyl, RDis an acety l rosuvastatin moiety, and REis a fenofibrate moiety’;(g) RAand RBare ethyl, RDis an acetyl rosuvastatin moiety, and REis a fenofibrate moiety;(h) RAand RBare tert-buty l, RDis an acetyl rosuvastatin moiety7, and REis a fenofibrate moiety7;(i) RAand RBare CsHn. RDis an acetyl rosuvastatin moiety7, and REis a fenofibrate moiety;(j) RAand RBare N-acetyl galactosamine moiety, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, RDis an acety l rosuvastatin moiety, and REis a fenofibrate moiety;(k) RAand RBare methyl, and Rc, and RDare an acetyl rosuvastatin moiety; (l) RAand RBare ethyl, and RDand REare an acetyl rosuvastatin moiety; (m) RAand RBare tert-buty l, and RDandREare an acety l rosuvastatin moiety7; (n) RAand RBare CsHu, and RDandREare an acetyl rosuvastatin moiety; (0) RAand RDare N-acetyl galactosamine moiety. L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and I is -OCH2CH2-, and RDandREare an acetyd rosuvastatin moiety7;(p) RA, RB, RD, andREare methyl;(q) RAand RBare ethyl, and RDand REare methyl;(r) RAand RBare tert-butyl, and RDand REare methyl;(s) RAand RBare CsHn, and RDand REare methyl; or(t) RAand RBare N-acetyl galactosamine moiety7, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and RDandREare methvl.

9. A compound of Formula (VII) or a pharmaceutically acceptable salt thereof:owherein RAand RBare each independently a substituted or unsubstituted alkyl group, N-acetylgalactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; L1and L2are each independently substituted or unsubstituted alkylene; RCis independently hydrogen, halogen, substituted or unsubstituted alkyl, or acetoxyvinyl; n is 0, 1, 2, 3, or 4. wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101. and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

10. The compound of claim 9, wherein RAand RBare each independently a substituted or unsubstituted C1-24 alkyl group, N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; Rcis independently hydrogen, halogen, substituted or unsubstituted C1-24 alkyl group, or acetoxyvinyl; and L1and L2are each independently substituted or unsubstituted C1-24alkyl group.

11. The compound of claim 9, wherein the compound of formula (VII) is a compound of Formula (VIIA):(VIIA) wherein RAand RBare each independently unsubstituted C1-24 alkyl group. N-acetyl galactosamine moiety, acetate, propionate, butyrate, a fibrate moiety, or a statin moiety; RCis independently hydrogen, halogen, unsubstituted C1-6alkyl, or acetoxyvinyl; and n is 0, 1, or 2.

12. The compound of claim 9, wherein RAand RBare each independently unsubstituted Ci-is alkyl group or N-acetyl galactosamine moiety.The compound of claim 9, wherein:(a) RAand RBare methyl, Rcis 5-Br, and n is 1;(b) RAand RBare methyl, Rcis 5-CH3, and n is 1;(c) RAand RBare methyl, Rcis 3,5-tert-butyl, and n is 2;(d) RAand RBare methyl, RCis 5-(1-acetoxyvinyl), and n is 1;(e) RAand RBare ethyl, R is 5-Br, and n is 1;(f) RAand RBare ethyl, RCis 5-CH3, and n is 1;(g) RAand RBare ethyl, Rcis 3,5-tert-butyl, and n is 2;(h) RAand RBare ethyl, Rcis 5 -(1 -acetoxy vinyl), and n is 1;(i) RAand RBare n-butyl and n is 0;(j) RAand RBare n-butyl, Rcis 5-Br, and n is 1;(k) RAand RBare n-butyl, Rcis 5-CH?, and n is 1;(l) RAand RBare n-butyl, Rcis 3,5-tert-butyl, and n is 2;(m) RAand RBare n-butyl, RCis 5-(1-acetoxyvinyl), and n is 1;(n) RAand RBare -CsHn and n is 0;(o) RAand RBare -CsHn, Rcis 5-Br, and n is 1;(p) RAand RBare -CsHi7, Rcis 5-CH3, and n is 1;(q) RAand RBare -CsHn, Rcis 3,5-tert-buty l, and n is 2;(r) RAand RBare -CsHn, RCis 5-(1-acetoxyvinyl), and n is 1;(s) RAand RBare N-acetyl-galactosamine moiety. L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 0;(t) RAand RBare N-acetyl galactosamine moiety, Rcis 5-Br, L1and L2are - CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is I;(u) RAand RBare N-acetyl galactosamine moiety, Rcis 5-CH3, L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 1;(v) RAand RBN-acetyl galactosamine moiety, Rcis 3,5-tert-butyl, L1and L2are -CH2-. R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 2; or(w) RAand RBare N-acetyl galactosamine moiety, Rcis 5-(l-acetoxyvinyl), L1and L2are -CH2-, R100, R101, and R102are -C(O)CH3, and L5is -OCH2CH2-, and n is 1.

14. A compound of Formula (I) or a pharmaceutically acceptable salt thereof:wherein R1is hydrogen, a butyrate, a fibrate moiety, or a statin moiety; R2is hydrogen, butyrate, a fibrate moiety, or a statin moiety; R3is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; and R4is hydrogen, acetate, propionate, butyrate, or N-acetyl galactosamine moiety; provided that R1, R2, R3, and R4are not simultaneously hydrogen; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

15. A pharmaceutical composition comprising an effective amount of a glycerol compound and a pharmaceutically acceptable excipient.

16. A compound of Formula (II) or a pharmaceutically acceptable salt thereof:wherein R1, R2, R3, and R4are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety; and L1, L2, L3, and L4are each independently hydrogen or substituted or unsubstituted alkylene;wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

17. A compound of Formula (IV) or a pharmaceutically acceptable salt thereof:R4O" B(OH)2(IV) wherein R3and R4are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine moiety, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety; and L3and L4are each independently hydrogen or substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH3, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

18. A compound of Formula (V) or a pharmaceutically acceptable salt thereof:wherein R1and R2are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety; provided that R1and R2are not simultaneously hydrogen; L1and L2are each independently hydrogen or substituted or unsubstituted alkylene; and R6and R7are independently hydrogen, unsubstituted Ci-6 alkyl, -Cl, -F, -Br, -I, or acetoxyvinyl; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH3, and L5is a bond, -O-. substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

19. A compound of Formula (VI) or a pharmaceutically acceptable salt thereof:OR5wherein R1and R2are each independently hydrogen, acetate, propionate, butyrate, N-acetyl galactosamine, N-acetyl galactosamine moiety, a fibrate moiety, or a statin moiety; provided that R1and R2are not simultaneously hydrogen; R5are each independently hydrogen or substituted or unsubstituted alkyl; and L1and L2are each independently hydrogen or substituted or unsubstituted alkylene; wherein the N-acetyl galactosamine moiety has the following structure:wherein R100, R101, and R102are each independently hydrogen or -C(O)CH₃, and L5is a bond, -O-, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.

20. A compound having the structure:oOAc tBu OAc OAcacceptable salt of any one of the foregoing, wherein R3and R4are independently a fibrate moiety or a statin moiety.

21. A pharmaceutical composition comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable excipient.

22. A method of reducing craving for sugar, reducing a craving for alcohol, treating a disease mediated by fibroblast growth factor 21, or treating citrin deficiency in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of claim 1.

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