28 results about "Sialoglycoprotein" patented technology

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.

An agent including a glycan-specific IgG antibody moiety, a cellular receptor binding moiety which binds to hepatocytes or other degrading cells through asialoglycoprotein (ASGPR) receptors of hepatocytes or other cell receptors which are on the surface degrading cells in a patient or subject, and optionally, a linker moiety connecting the glycan-specific IgG antibody moiety and the cellular receptor binding moiety.

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.

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 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 present application relates to the technical field of food processing, in particular to a solid beverage based on edible bird's nest sialic acid derivative and a preparation method thereof, which solves the problems of single functional factor, poor stability and poor brewing property in existing intelligence drinks; by using edible bird's nest stewing material as a natural nutritional wall material, the sialic acid-glycoprotein therein and algal oil form an intelligence "synergistic functional matrix", produce an enhancing effect, and combined with freeze-drying and low-temperature fluidized bed granulation technology, the low-temperature stable embedding of active components is realized, the intelligence activity of nutritional factors of the product, the storage stability and the use convenience are improved, and the product is suitable for brain health conditioning and daily supplement of different people.

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.

The invention provides an antibody for resisting an asialoglycoprotein receptor as well as a preparation method and application of the antibody. The antibody for resisting the asialoglycoprotein receptor comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises a heavy chain variable region HCDR1-HCDR3; and the light chain variable region comprises a light chain variable region LCDR1-LCDR3. According to the present invention, the affinity of the anti-asialoglycoprotein receptor antibody to the human asialoglycoprotein receptor is 0.425 nM, and the antigen recognition ability is strong; the compound disclosed by the invention can be used for remarkably inhibiting the DNA expression of HBsAg, HBeAg and HBV of HepG2.2. 15 cells and HepAD38 cells, has a function of inhibiting the replication of the hepatitis B virus, and has a great application prospect in medicines for preventing and / or treating hepatitis B virus infection and / or preventing and / or treating related diseases caused by the hepatitis B virus infection.

A composition of matter including a deglycosylated IgA-binding moiety, a cellular receptor-binding moiety that binds to hepatocytes or other degrading cells through asialoglycoprotein receptors (ASGPR) on the surface of hepatocytes or other degrading cells in a patient or subject, and optionally, a linker moiety connecting deglycosylated IgA-binding moiety and the cellular receptor-binding moiety, wherein the composition of matter is useful for removing galactose-deficient IgA1 in a patient or subject.

Provided herein are a complex for diagnosing non-alcoholic steatohepatitis, use of the complex, and a contrast agent comprising the complex. The complex for diagnosing non-alcoholic steatohepatitis comprises hexa-lactoside, a metal chelator coupled to the hexa-lactoside, and a radionuclide labeling the metal chelator. The complex is capable of binding to an asialoglycoprotein receptor, so that the complex has potential for use as a radiological diagnostic agent.

The present invention provides an antisense oligomer having the base sequence depicted in SEQ ID NO: 26, an antisense oligomer having a base sequence resulting from substitution, deletion, insertion, or addition of 1 to 6 bases in the base sequence depicted in SEQ ID NO: 26, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable hydrate thereof, an oligonucleotide conjugate in which the antisense oligomer is bound with a molecule capable of binding to an asialoglycoprotein receptor, and a pharmaceutical composition containing the same.

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 directed to the bifunctional compounds and the use of such bifunctional compounds to lower plasma levels of extracellular target molecules by lysosomal degradation. Such bifunctional compounds have a cell surface receptor ligand covalently linked to a ligand that is capable of binding to an extracellular target molecule (such as a ligand for a growth factor, a cytokine, a chemokine, a hormone, a neurotransmitter, a capsid, a soluble receptor, an extracellular secreted protein, an antibody, a lipoprotein, an exosome, a virus, a cell, or a plasma membrane protein), where the cell surface receptor is associated with receptor mediated endocytosis, including asialoglycoprotein receptor (ASGPR) mediated lysosomal degradation and mannose-6-phosphate (M6PR) mediated lysosomal degradation. Pharmaceutical compositions comprising such bifunctional compounds and methods of treating a disease or disorder mediated by an extracellular molecule using such bifunctional compounds are also provided herein.

Application of a multifunctional supramolecular nanoplatform drug: The application of a multifunctional supramolecular nanoplatform in the preparation of drugs for liver ischemia-reperfusion injury. The multifunctional supramolecular nanoplatform is a GalAC4A supramolecular carrier loaded with naringenin (NAR). The multifunctional supramolecular nanoplatform is prepared from naringenin (NAR), galactose (Gal), and CAC4A from azocalixarene. The multifunctional supramolecular nanoplatform is a NAR@GalAC4A nanocomposite. The multifunctional supramolecular nanoplatform achieves hepatocyte-specific targeting through desialyl glycoprotein receptor-mediated endocytosis. This invention proposes a novel "receptor recognition-hypoxia response-synergistic therapy" three-pronged design strategy, successfully constructing a GalAC4A supramolecular carrier loaded with naringenin (NAR) to form a NAR@GalAC4A nanocomposite.

The invention discloses a diarylboronic acid-catechin drug-loaded aggregate with high stability and antioxidant activity and application, diarylboronic acid molecules exist in a positive charge participated interaction aggregate form, and boric acid groups are exposed on the outer surface of the aggregate. Catechin reacts with boric acid groups on the surface of the aggregate to generate dynamic covalent bond boric acid ester, the form of the aggregate is not changed, and finally the diarylboronic acid-catechin drug-loaded aggregate with high stability and antioxidant activity is obtained. The natural antioxidant catechin in the diarylboronic acid-catechin drug-loaded aggregate can be used as a health care and therapeutic drug or an auxiliary therapeutic drug to be conveyed in vivo, remove oxygen free radicals harmful to health and release antioxidant activity at tumor sites with overexpressed H2O2 or sialoglycoprotein.

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

The present disclosure provides lysosomal targeting bifunctional molecules that target anti-MuSK autoantibodies that cause disease for degradation. The lysosomal targeting bifunctional molecule comprises a ligand moiety that specifically binds to an asialoglycoprotein receptor (ASGPR), and the ligand moiety is linked via a carrier protein to a muscle-specific kinase (MuSK) polypeptide that specifically binds to a target anti-MuSK autoantibody.

The invention discloses a preparation method and application of a dual-targeting hepatocellular carcinoma nano-drug, and belongs to the field of biological medicines. According to the invention, a double-targeting target molecule with myeloperoxidase-asialoglycoprotein receptor double-targeting property is synthesized, and the double-targeting target molecule is modified on a covalent organic nano molecule COF-366 through pi-pi stacking, wherein the covalent organic nano molecule COF-366 is coated with chemotherapeutic drugs sorafenib and chloroquine and has photodynamic characteristics. The obtained nano-drug can be gradually delivered to hepatocytes under the guidance of double-targeting molecules, drug release is started in acidity of a tumor acidic microenvironment, the synergistic treatment effect of photodynamic therapy and chemotherapy can be played, and the synergistic effect causes tumor injury, so that the inflammation targeting of the nano-drug is further enhanced. The nano-drug has good stability and biological safety, in-vivo behavior tracing and treatment efficacy evaluation are carried out in subcutaneous solid tumor and in-situ tumor mouse models, and the nano-drug is expected to play a huge role in clinical application.

The invention relates to a GalNAc derivative and an oligonucleotide conjugate thereof as well as a preparation method and application of the GalNAc derivative and the oligonucleotide conjugate, the novel GalNAc derivative has a liver targeting delivery effect and has high affinity with an asialoglycoprotein receptor ASGPR, and due to the structural design, the synthesis method of the GalNAc derivative is simple in process, convenient to operate and beneficial to large-scale industrial production and application. Therefore, the synthesis and large-scale production difficulty and cost are obviously reduced compared with those of the trident GalNAc derivative (such as L96). Meanwhile, the effect of the oligonucleotide conjugate containing the GalNAc ligand is better than that of oligonucleotide conjugates containing an L96 ligand and other similar positive reference ligands.

The present invention provides a composition and method for treating an allergic disease. The composition comprises a ligand for asialoglycoprotein receptor 1 (Asgr1). The allergic disease may be atopic dermatitis, allergic rhinitis, urticaria, allergic asthma, allergic conjunctivitis, allergic gastrointestinal inflammation, or anaphylactic shock. The allergic disease may be caused by house dust mites. The present invention also provides a method for determining if a test compound activates human Asgr1.

Provided is an oligonucleotide conjugate comprising an oligonucleotide and two or more linearly connected asialoglycoprotein receptor-binding molecules attached to the oligonucleotide, wherein the oligonucleotide comprises a locked nucleoside analog having a bridging structure between the 4′ and 2′ positions, is complementary to a human PCSK9 gene, and has inhibitory activity on the expression of the human PCSK9 gene. The oligonucleotide conjugate of the present invention can be used in the field of pharmaceutical products, in particular, the field of the development and production of therapeutic agents for diseases associated with a high LDL cholesterol level.

Provided herein are compounds having structures (I), (II), (III) or (IV) wherein in these structures (I), (II), (III) and (IV), each R1 is independently selected from aliphatic alkyl C4-C100 groups, which are 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 alkali metal ions, alkaline earth metal ions or primary, secondary or tertiary ammonium ions; and m, p and s are independently selected from integers of 1 to 120. The compounds are useful as therapeutic agents targeting liver asialoglycoprotein receptors in the form of lipid nanoparticles, liposomes or micelles including drugs or oligonucleotides.