77 results about "Glucagon receptor" patented technology

A pharmaceutical composition comprises a GPCR agonist fusion protein in which a GPCR agonist peptide is covalently coupled to albumin via a linker in a manner that is resistant to a retro-Michael addition. Advantageously, compositions presented herein avoid decoupling of the agonist form the albumin while retaining the agonist in a steric relationship to the albumin that allows for effective binding and activation of the GPCR while also enabling gp60-mediated transcytosis and FcRn-mediated albumin recycling. These properties enable ultra-low dosages for the GPCR agonist fusion protein to give a therapeutic effect while substantially reducing or even entirely avoiding adverse effects otherwise commonly associated with unbound agonists. Such retro-Michael resistant composition is generally achieved by conformational modification of the albumin, resulting in stereoselective coupling of the linker to the albumin.

A pharmaceutical composition comprises a GPCR agonist fusion protein wherein the GPCR agonist peptide is covalently conjugated to an albumin via a linker in a manner that is resistant to a reverse Michael addition. Advantageously, the compositions presented herein avoid uncoupling of the agonist to the albumin while maintaining the agonist and the albumin in a spatial relationship that allows efficient binding and activation of the GPCR while also enabling gp60-mediated endocytosis transport and FcRn-mediated albumin recirculation. These characteristics enable ultra-low doses of GPCR agonist fusion proteins to produce therapeutic effects while significantly reducing or even completely avoiding side effects that would otherwise be typically associated with unbound agonists. Such reverse Michael resistant compositions are typically achieved by conformationally modifying an albumin, resulting in a stereoselective coupling of a linker to the albumin.

Incretin analogs are provided that have activity at each of the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors. The incretin analogs have structural features resulting in balanced activity and extended duration of action at each of these receptors. Methods also are provided for treating diseases such as type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and obesity.

A pharmaceutical composition comprises a GPCR agonist fusion protein in which a GPCR agonist peptide is covalently coupled to albumin via a linker in a manner that is resistant to a retro-Michael addition. Advantageously, compositions presented herein avoid decoupling of the agonist form the albumin while retaining the agonist in a steric relationship to the albumin that allows for effective binding and activation of the GPCR while also enabling gp60-mediated transcytosis and FcRn-mediated albumin recycling. These properties enable ultra-low dosages for the GPCR agonist fusion protein to give a therapeutic effect while substantially reducing or even entirely avoiding adverse effects otherwise commonly associated with unbound agonists. Moreover, these properties also enable transport of the GPCR agonist fusion protein across the blood brain barrier and therefore allow treatment of neural disorders.

Provided herein are methods for treating obesity or diabetes by administering a 15- PGDH inhibitor to a subject. In some cases, the methods provided herein additionally involve administering to a subject an agent selected from the group consisting of: a glucagon- like peptide- 1 (GLP-1) receptor agonist, a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, a glucagon receptor agonist, a GLP-1 receptor / GIP receptor co- agonist, a GLP-1 receptor agonist / GIP receptor antagonist, a GLP-1 receptor / glucagon receptor co-agonist, a GLP-1 receptor / GIP receptor / glucagon receptor triple agonist, a GLP-1 receptor / GLP-2 receptor co-agonist, a combination of a GLP-1 receptor agonist and an amylin receptor agonist.

Disclosed herein is a compound of formula (I): (I), or a pharmaceutically acceptable salt thereof. Also disclosed herein is a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive. Further disclosed herein is a method for preventing or treating a disease or condition through the modulation of the glucagon receptor using a compound of formula (I), or a pharmaceutically acceptable salt thereof.

The application discloses a glucagon peptide-1 and glucagon receptor dual-agonistic polypeptide and application thereof, and the polypeptide structure is shown in the following general formula (I). The dual-agonistic polypeptide has dual-agonistic activity on human GLP-1 and glucagon receptors. The GLP-1 / glucagon receptor dual-agonistic polypeptide can effectively reduce blood sugar and weight, and has obvious lipid-regulating effect. The GLP-1 / glucagon receptor dual-agonistic polypeptide is stable in vivo, and is suitable to be used as an active component of drugs for diabetes, obesity, hyperlipidemia and the like.

The present invention relates to a use of a novel triple activator, having activity on all of GLP-1, GIP, and glucagon receptors, for preventing or treating lipid metabolic diseases.

Incretin analogs and their use. It contains a triple-acting agent protein for human glucose-dependent insulinotropic polypeptide (GIP) receptor, glucagon-like peptide-1 (GLP-1) receptor and glucagon (GCG) receptor, and is useful for the treatment of type 2 diabetes (T2D), obesity, non-alcoholic fatty liver disease (NAFLD) and other carbohydrate and lipid metabolism disorders.

The present invention is entitled Triple Agonists at the Glucagon / GLP-1 / GIP Receptor. The present invention relates to triple agonists that are active at all of the glucagon, GLP-1 and GIP receptors and uses thereof.

The present disclosure relates to peptide compounds which are dual or tri-agonists of the human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), the human glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR), and / or the human glucagon receptor (GCGR). The invention also relates to peptide compounds that are suitable for oral administration. These peptide compounds of the invention may be useful in the treatment of type 2 diabetes mellitus (T2DM) and obesity.

Provided herein are incretin analog compounds that are GLP-1 / GIP / Gcg receptor triple agonists and their medical use in the treatment and / or prevention of a disease such as dyslipidemia, fatty liver disease, metabolic syndrome, MASH, MAFLD, obesity and T2DM.

Disclosed herein are compounds of formula (I): (I), or a pharmaceutically acceptable salt thereof. Also disclosed herein is a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive. Further disclosed herein is a method for preventing or treating a disease or condition through the modulation of the glucagon receptor using a compound of formula (I), or a pharmaceutically acceptable salt thereof.

The present invention provides a glucagon analogue containing β - amino acids or a pharmaceutically acceptable salt thereof and its application. By replacing α - amino acids with corresponding β - amino acids at different amino acid sites, the glucagon analogue of the present invention has a glucagon receptor (GCGR) agonistic potency equivalent to or higher than that of natural glucagon, and at the same time has significantly improved plasma stability and liver microsome stability, and thus has better drug - like properties.

The present invention relates to a use of a novel triple agonist having activities for all of GLP -1, GIP, and glucagon receptors for preventing or treating diabetes.

Provided herein are compositions with viral vectors that mediate overexpression of Gastric Inhibitory Polypeptide Receptor (GIPR), a Glucagon Receptor (GCGR), or a Glucagon-Like Peptide 1 Receptor (GLP-1R), or ligands thereof in adipocytes. Also provided here are methods of treating obesity and other metabolic disorders using these compositions.

A polypeptide that is active against each of a GIP, a GLP-1, and a glucagon receptor is provided. The polypeptides have structural features that result in each of the receptors having activity and extended action time. Also provided are methods for treating diseases and / or conditions such as obesity, long term weight management, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), dyslipidemia, metabolic syndrome, chronic kidney disease (CKD), osteoarthritis (OA), obesity-associated sleep apnea (OSA), and polycystic ovarian syndrome (PCOS).

Disclosed herein are polypeptides having activity as agonists of a glucagon receptor (“GCGR”), molecules comprising such polypeptides and a half-life extending domain (e.g., an Fc-containing polypeptide), including molecules comprising an antibody that specifically binds to a glucose-dependent insulinotropic polypeptide receptor (“GIPR”), pharmaceutical compositions comprising such polypeptides and molecules, and methods of using such polypeptides, molecules, and pharmaceutical compositions in weight management and the treatment of certain disorders such as obesity.

Disclosed herein is a compound of formula (I): or a pharmaceutically acceptable salt thereof. Also disclosed herein is a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive. Further disclosed herein is a method for preventing or treating a disease or condition through the modulation of the glucagon receptor using a compound of formula (I), or a pharmaceutically acceptable salt thereof.

The present disclosure provides a compound and use thereof as a glucagon receptor antagonist. The compound includes a compound A, or an isomer, metabolite, prodrug, pharmaceutically acceptable ester, or pharmaceutically acceptable salt of the compound A. The glucagon receptor antagonist in the present disclosure has a novel skeleton structure and a low half maximal inhibitory concentration on the glucagon receptor.

Disclosed herein is a compound of formula (I): or a pharmaceutically acceptable salt thereof. Also disclosed herein is a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive. Further disclosed herein is a method for preventing or treating a disease or condition through the modulation of the glucagon receptor using a compound of formula (I), or a pharmaceutically acceptable salt thereof.

Provided herein are compositions with viral vectors that mediate overexpression of Gastric Inhibitory Polypeptide Receptor (GIPR), a Glucagon Receptor (GCGR), or a Glucagon-Like Peptide 1 Receptor (GLP-1R), or ligands thereof in adipocytes. Also provided here are methods of treating obesity and other metabolic disorders using these compositions.

This invention relates to a polypeptide compound and its applications, and more specifically, to a dual or triple agonist polypeptide drug that activates glucagon-like peptide-1 receptor and optionally glucose-dependent insulinotropic peptide receptor and glucagon receptor, and its application in the treatment of metabolic syndrome.

The present invention relates to the medical use of specific long-acting glucagon analogues having dual GLP-1 / glucagon receptor agonist activity in the prevention and / or treatment of metabolic liver disease, particularly non-alcoholic fatty liver disease (NAFLD), non- alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), NAFLD-associated liver fibrosis and / or cirrhosis.

The present invention provides pharmaceutically acceptable controlled-release microparticle composition(s) and formulation(s) comprising said composition(s) for use in the treatment of obesity, diabetes, or both. The composition(s) and formulation(s) described herein comprise microparticles comprising API(s) and biodegradable polymer compounds. The API(s) of the composition(s) and formulation(s) described herein exhibit detectable or significant agonist activity for one or more of the melanocortin-1 receptor (MC1), melanocortin-2 receptor (MC2), melanocortin-3 receptor (MC3), melanocortin-4 receptor (MC4), and melanocortin-5 receptor (MC5), GLP-1 receptor, glucagon receptor, and GIP receptor, and generally have a molecular weight of at least about 1000 Da.

The invention relates to the field of medical biology, in particular to a tri-agonist polypeptide compound which has triple agonist activity on a glucagon-like peptide-1 receptor (GLP-1 R), a glucose-dependent insulinotropic polypeptide receptor (GIP R) and a glucagon receptor (GCG R) and is shown in a general formula (I) or salt or solvate of the tri-agonist polypeptide compound, and relates to application of the tri-agonist polypeptide compound in treatment of metabolic syndromes.

The present invention relates to GLP-1 receptor agonist compounds having an additional agonist activity over the GIP receptor and / or an agonist activity over the glucagon receptor and / or an antagonist activity over the GIP receptor for use in the treatment of joint diseases and / or joint pain and selected from the group comprising retatrutide, tirzepatide, orforglipron, mazdutide, efinopegdutide, froniglutide, maridebart cafraglutide, survodutide, efpeglenatide, ecnoglutide, efocipegtrutide and UBT251. The invention also relates to a pharmaceutical composition comprising at least one of the above mentioned GLP-1 receptor agonist compound, and a pharmaceutically acceptable excipient, for use in the treatment of joint diseases and / or joint pain.

The invention provides a GLP-1R / GIPR / GCGR triple receptor agonist and an application of the GLP-1R / GIPR / GCGR triple receptor Specifically, the invention provides a polypeptide with GLP-1 (glucagon-like peptide-1) R / GIPR / GCGR triple receptor agonist activity or a pharmaceutically acceptable salt thereof, and the polypeptide or the pharmaceutically acceptable salt thereof has obvious triple agonist activity of a glucagon-like peptide-1 (GLP-1) receptor, a gastric inhibitory polypeptide (GIP) receptor and a glucagon (GCG) receptor. The compound can be used for preparing pharmaceutical compositions for preventing or treating metabolic diseases such as type I diabetes mellitus, type II diabetes mellitus, gestational diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia and the like.

A pharmaceutical composition comprises a GPCR agonist fusion protein in which a GPCR agonist peptide is covalently coupled to albumin via a linker in a manner that is resistant to a retro-Michael addition. Advantageously, compositions presented herein avoid decoupling of the agonist form the albumin while retaining the agonist in a steric relationship to the albumin that allows for effective binding and activation of the GPCR while also enabling gp60-mediated transcytosis and FcRn-mediated albumin recycling. These properties enable ultra-low dosages for the GPCR agonist fusion protein to give a therapeutic effect while substantially reducing or even entirely avoiding adverse effects otherwise commonly associated with unbound agonists. Moreover, these properties also enable transport of the GPCR agonist fusion protein across the blood brain barrier and therefore allow treatment of neural disorders.

Disclosed herein is a preserved liquid pharmaceutical formulation comprising a amylin receptor agonist, a GLP-1 receptor agonist, a hydroxypropyl-substituted cyclodextrin, and one or more preservatives. The co-formulation can be used for medical treatment of subjects with: overweight or obesity, with or without associated co-morbidities; diabetes, with or without associated co-morbidities; and cardiovascular disease.