60 results about "Asialoglycoprotein receptor" patented technology

The present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

The disclosure describes compounds of Formula (I) and Formula (II), which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-β1AR binding moiety. Compounds of Formula (I) and Formula (II) are useful in preventing, treating and / or ameliorating heart failure in a subject when administered therapeutically effective amounts.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Extracellular protein degraders and compositions are provided that have a potent asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an Extracellular Protein Targeting Ligand for the selective degradation of the Target Extracellular Protein, for example immunoglobulin in vivo to treat disorders mediated by the extracellular protein.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

The present disclosure provides lysosomal targeting bifunctional molecules that target disease causing anti-TSHR autoantibodies for degradation. The lysosomal targeting bifunctional molecules include a ligand moiety that specifically binds to an asialoglycoprotein receptor (ASGPR), and which is linked via a carrier protein to a thyroid stimulating hormone receptor (TSHR) polypeptide that specifically binds target anti-TSHR autoantibodies.

A compound having the structure (I), (II), (III), or (IV) is provided: (I), (II), (III), (IV) ) where in these structures, (I), (II), (III), and (IV), each R1 is independently selected from aliphatic alkyl C4-C100 groups optionally substituted with one or more of alkenyl, alkynyl, hydroxyl, amide, ester, and / or ether groups; R2 is selected from [-OCH2CH2-]p or (A); R3 is selected from Formula (V) and Formula (VI): (V, (VI). M+ is selected from an alkali metal ion, an alkaline earth metal ion, or a primary, secondary or tertiary ammonium ion; and m, p, and s are independently selected from integers from 1 to 120. The compound is useful as a liver asialoglycoprotein receptor-targeted therapeutic agent in the form of a lipid nanoparticle, a liposome or a micelle including a drug or oligonucleotide.

The invention discloses a method for detecting the assembly change of an ASGPR (asialoglycoprotein receptor) on the surface of a hepatocyte, which comprises the following steps: carrying out specific labeling on the ASGPR on the surface of the hepatocyte through an antibody, and carrying out fluorescence imaging on the ASGPR on the surface of a cell membrane, the purpose of detecting ASGPR assembly change on the liver cell membrane is achieved by statistically analyzing the number of ASGPR protein positioning points on the surface of the cell membrane and aggregation parameters. According to the method, the distribution and aggregation condition of the ASGPR on the cell surface is measured through the nanoscale resolution, the change of the ASGPR in the cell membrane assembly relation is detected, damage to sample cells is small, the time cost of the experimental process is small, protein positioning is accurate, and as the ASGPR is an endocytosis receptor specifically existing on the surface of hepatocellular carcinoma cells, the detection result is accurate, and the detection accuracy is high. Efficient treatment can be achieved through a drug delivery system formed by targeting ASGPR, ASGPR can be better known by observing the assembly difference of ASGPR on the surface of a cell membrane from the nanoscale, and the method has wide application prospects in the field of medical detection and diagnosis.

The invention discloses a substance composition. The present invention relates to a conjugate comprising a deglycosylated IgA-binding moiety, a cell receptor-binding moiety that binds to a hepatocyte or other degraded cell of a patient or subject through an asialoglycoprotein receptor (ASGPR) on the surface of the hepatocyte or other degraded cell, and optionally a linker moiety that links the deglycosylated IgA-binding moiety and the cell receptor-binding moiety, wherein the composition of matter can be used to remove galactose deficient IgA1 in a patient or subject.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Provided is an accurate guide RNA (gRNA) screening method for base editing of an asialoglycoprotein receptor 1 (ASGR1) gene, including the following steps: (1) gRNA design; (2) primer design; (3) in vitro transcription of gRNA; (4) cell transfection; (5) collection of cells, and extraction and polymerase chain reaction (PCR) of a genome; and (6) Sanger sequencing.

Extracellular protein degraders and compositions with improved pharmacokinetic properties are provided that have a potent asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an Extracellular Protein Targeting Ligand for the selective degradation of the Target Extracellular Protein, for example immunoglobulin in vivo to treat disorders mediated by the extracellular protein.

Provided is a modified regulatory T cell capable of recognizing cells of the liver, capable of treating and / or preventing transplant rejection or immune-mediated damage, and capable of promoting regeneration of cells of the liver.SOLUTION: The present invention provides engineered regulatory T cells (Tregs) comprising a chimeric antigen receptor (CAR), wherein said CAR comprises an antigen recognition domain that specifically binds to the asialoglycoprotein receptor (ASGR). The invention also provides a method of promoting liver tissue repair and / or regeneration in a subject, said method comprising administering to said subject a modified Treg comprising a CAR, or a pharmaceutical composition comprising said modified Treg, wherein said CAR comprises a liver-specific antigen recognition domain.SELECTED DRAWING: None

This invention provides extracellular protein degraders and compositions that have an asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an Extracellular Protein Targeting Ligand for the selective degradation of the Target Extracellular Protein for example an immunoglobulin or other extracellular protein in vivo to treat disorders mediated by that protein.

The application belongs to the technical field of biological medicine, and particularly relates to a galactosamine-doxetaxel conjugate as well as a preparation method and application thereof. First, doxetaxel and 3,3'-diseleno-dipropionic acid are used as raw materials, and after heating reaction, 3,3'-diseleno-dipropionic acid doxetaxel is obtained. Then, the obtained 3,3'-diseleno-dipropionic acid doxetaxel and galactosamine are used as raw materials, and after heating reaction, galactosamine-3,3'-diseleno-dipropionic acid doxetaxel conjugate is obtained through column chromatography separation and purification. The obtained conjugate can be specifically recognized by endogenous lectin receptors (such as asialoglycoprotein receptor ASGPR) which are highly expressed on the surface of hepatoma cells, so as to be taken up by hepatoma cells through a receptor-mediated pathway, and has application prospect in the direction of hepatoma targeted treatment.

In this specification, Disclosed herein are binding polypeptides that bind to asialoglycoprotein receptor 1 (ASGR1) and methods of using same to induce immune tolerance to an antigen of interest, e.g., to treat, ameliorate, inhibit, or prevent a disease or disorder associated with an unwanted immune response to an antigen of interest, such as an autoimmune disease.

The invention relates to an anti-inflammatory and lipid-lowering-based nano preparation for treating fatty liver and a preparation method of the nano preparation. Galactose modified polyethylene glycol-polylactic acid-glycolic acid copolymer (PEG-PLGA) is used as a targeting carrier, and a lipid-lowering drug fenofibrate and an anti-inflammatory drug curcumin are co-loaded; the particle size of the nano preparation is 150-200nm, and the drug encapsulation efficiency is greater than or equal to 85%. Galactose modified PEG-PLGA is adopted as a carrier, galactose can be specifically combined with an asialoglycoprotein receptor (ASGPR) specifically expressed on the surface of liver cells, active targeting of the liver is achieved, the drug enrichment amount of the liver lesion position is remarkably increased, meanwhile, accumulation of drugs in extrahepatic tissue is reduced, extrahepatic toxicity is effectively reduced, and the drug delivery effect is improved. According to the present invention, the anti-inflammatory drug curcumin and the fenofibrate are combined, such that the biological safety of the preparation is improved, the lipid lowering drug fenofibrate and the anti-inflammatory drug curcumin are innovatively co-loaded, and the fenofibrate and the anti-inflammatory drug curcumin form the synergistic effect system: fenofibrate can activate peroxisome proliferator-activated receptor alpha (PPAR alpha), promote liver lipid catabolism, and reduce lipid deposition;

The invention relates to the technical field of liver targeting compounds, in particular to a cyclic peptide ligand of a targeting asialoglycoprotein receptor, pharmaceutically acceptable salt of the cyclic peptide ligand, application of the pharmaceutically acceptable salt and a pharmaceutical composition. The invention provides a cyclic peptide ligand of a targeted asialoglycoprotein receptor, a pharmaceutically acceptable salt of the cyclic peptide ligand, an application of the pharmaceutically acceptable salt and a pharmaceutical composition. The cyclic peptide ligand has better endocytosis activity.

The invention relates to an application of a multifunctional supramolecular nano-platform drug, in particular to an application of a multifunctional supramolecular nano-platform in preparation of a drug for treating liver ischemia reperfusion injury. The multifunctional supramolecular nano platform is a GalAC4A supramolecular carrier loaded with naringenin NAR. The multifunctional supramolecular nano platform is prepared from naringenin NAR, galactose Gal and CAC4A in azo calixarene. The multifunctional supramolecular nano platform is a nano compound of NAR (at) GalAC4A. The multifunctional supramolecular nano platform realizes specific targeting of hepatocytes through endocytosis mediated by an asialoglycoprotein receptor. The invention provides a novel'receptor recognition-hypoxia response-collaborative treatment ', a three-party design strategy is provided, a GalAC4A supermolecular carrier loaded with naringenin (NAR) is successfully constructed, and the NAR-coated GalAC4A nano-composite is formed.

Conjugates that target an asialoglycoprotein receptor, such as in the liver, and comprise an active agent (e.g., a therapeutic or an imaging agent) and rigid linker components; pharmaceutical compositions; and methods of use in the delivery of conjugates, and the imaging and treating of the liver (e.g., in a subject with NASH) with conjugates.

The present invention is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor. Pharmaceutical compositions based upon these bifunctional small molecules represent an additional aspect of the present invention. These compounds and / or compositions may be used to treat disease states and conditions by removing circulating proteins through degradation in the hepatocytes or macrophages of a patient or subject in need of therapy. Methods of treating disease states and / or conditions in which circulating proteins are associated with the disease state and / or condition are also described herein.

The invention discloses an oligonucleotide pharmacobiological analysis system based on a GalNAc technology, and relates to the technical field of drug analysis, and the oligonucleotide pharmacobiological analysis system is technically characterized in that in a GalNAc conjugate coupling delivery module, a coupling unit covalently couples an oligonucleotide drug and a GalNAc-trimer through a click chemical reaction to form a liver-targeted delivery carrier; the targeting unit is specifically combined with an asialoglycoprotein receptor on the surface of a hepatocyte by utilizing the vector to realize endocytosis; in the RT-qPCR quantitative analysis module, a magnetic separation purification unit adsorbs oligonucleotides by using carboxylated magnetic beads; the reverse transcription unit uses a stem-loop primer to convert oligonucleotide into cDNA (complementary deoxyribonucleic acid) under the action of heat-resistant reverse transcriptase; the fluorescence quantification unit adopts an FAM-labeled TaqMan probe to monitor amplification, and the absolute concentration of the medicine is calculated in combination with a standard curve; according to the invention, the technical problems of poor targeting, serious off-target effect and poor stability are solved, and high-quality drug effect evaluation can be carried out.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

The present disclosure relates to bifunctional small molecules that include a circulating protein binding moiety (CPBM) linked through a linker group to a cell receptor binding moiety (CRBM) that is a membrane receptor of a degradative cell, such as a hepatocyte or other degradative cell. In a particular embodiment, (CRBM) is a moiety that binds to the asialoglycoprotein receptor of a hepatocyte (asialoglycoprotein receptor binding moiety, or ASGPRBM). In a further embodiment, (CRBM) is a moiety that binds to the receptor of other cells that can degrade proteins, such as LRP1, LDLR, FcγRI, FcRN, transferrin, or macrophage scavenger receptor. TIFF2025509730000520.tif99145

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-β1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and / or ameliorating heart failure in a subject when administered in therapeutically effective amounts.

The present invention is based on the discovery of a proteolysis targeting compound having tissue targeting capability and use thereof, relating to medicinal products, and to such a compound or a pharmaceutically acceptable salt thereof, a stereoisomer, a solvate, or a polymorph. The compound is a proteolysis targeting chimera (PROTAC) with specific tissue targeting ability. The compound structure comprises three parts, i.e., A-BD-CON, wherein the part A is a PROTAC, one end of the structure thereof is a target protein ‘binding ligand, and the other end is a ubiquitin ligase ligand; and the part CON is a ligand of an asialoglycoprotein receptor (ASGPR), enabling the specific tissue targeting function. The compound enriches in liver tissue and is able to target cells in the tissue. The invention achieves improved druggability of the PROTAC with higher solubility and cellular membrane permeability, therefore produces enhanced pharmaceutical effect on the specific target tissue.

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-β1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and / or ameliorating heart failure in a subject when administered in therapeutically effective amounts.

The present invention relates to an RNAi construct for inhibiting the expression of an asialoglycoprotein receptor 1 (ASGR1) gene, a pharmaceutical composition comprising the same, and uses thereof. The RNAi construct achieves the purpose of disease prevention and / or treatment by inhibiting expression of the ASGR1 gene in the liver.