89 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.

The invention relates to the technical field of biological medicine, and discloses an intestinal insulinotropic analogue with multiple biological activities, a synthesis method, a pharmaceutical composition and application, the synthesized intestinal insulinotropic analogue has triple agonist activity of a GLP-1 receptor, a glucagon receptor and a CCK-1 receptor, not only has the treatment effect of GLP-1 on diabetes, but also has the treatment effect of GLP-1 on CCK-1, and also has the effect of GLP-1 on CCK-1 on CCK-1. The traditional Chinese medicine composition also has the regulating effect of glucagon on lipolysis and energy metabolism and the beneficial effect of CCK on appetite inhibition, so that a synergistic effect is generated on sugar, fat and energy metabolism; the application has great potential in preparation of drugs for treating metabolic syndromes, such as diabetes, obesity, non-alcoholic fatty liver diseases, dyslipidemia and other diseases.

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 is a tri-agonist polypeptide compound targeting a GLP-1 receptor, a glucagon receptor and a GIP receptor, wherein the polypeptide compound can selectively act on the GLP-1 receptor, the glucagon receptor and the GIP receptor, so as to exert the activities of GLP-1, glucagon and GIP at the same time, and the polypeptide compound has a unique agonistic activity proportion for the three receptors, thus achieving better glucose reduction, weight reduction and lipid regulation effects.

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.

The present application relates to the pharmaceutical and biological fields, particularly relates to a polypeptide compound of general formula (I) with triple agonist activity on glucagon like peptide-1 receptor (GLP-1 R), glucose-dependent insulinotropic polypeptide receptor (GIP R), and glucagon receptor (GCG R), and use thereof in the treatment of metabolic syndrome.

Provided are various embodiments relating to a GLP1R agonist or a dual agonist that specifically binds canine, feline, and / or equine GLP1R, or Glucagon receptor / G1PR. Such agonists can be used alone or in combination in methods to treat canine, feline, and / or equine metabolic disorders, such as high glucose, obesity, osteoarthritis, improved cardiovascular outcomes, and for the extension of healthy aging.

The present invention provides a combination therapy comprising: a compound I (GLP-1R / glucagon receptor dual agonist): H-His-Ac4c-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Leu-Asp-Glu-Arg-Ala-Lys-Asp-Phe-Lys (HOOC-(CH2) 16-CO-gamma Glu-Gly-Ser-Gly-Gly-Gly-)-Trp-Leu-Glu-Ser-Ala-NH2 (I), and a long acting NPY2 receptor agonist selected from the group consisting of compounds A to L. The invention further relates to a method for preparing the same. The combination therapy may be used to treat obesity and various obesity-related conditions, diseases, or co-diseases such as type 2 diabetes, liver diseases such as NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis), kidney diseases, or cardiovascular diseases.

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.

The invention herein provides pharmaceutically acceptable, controlled-release microparticle composition(s) and formulation(s) comprising such composition(s) for use in the treatment of obesity, diabetes, or both. Composition(s) and formulation(s) herein comprise microparticles comprising API(s) and biodegradable polymer compound(s). API(s) of composition(s) and formulation(s) herein demonstrate detectable or significant agonist activity against one or more of 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 typically have a molecular weight of at least about 1000 Da.

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).

The invention provides an insulinotropic polypeptide analogue and application thereof, and relates to the technical field of polypeptide preparation and application thereof. The intestinal insulinotropic polypeptide analogue comprises a co-agonist, the co-agonist is GLP-1, GIP and GCG three-receptor co-agonist polypeptide which is in acylation connection with a fatty acid side chain, and the amino acid sequence of the polypeptide or a salt thereof or a solvate thereof is shown as the following formula: Y (Aib) QGTFTSDX10SIX13LDX16X17AQ (Aib) X21FIX24X25LX27EGGPSSGAPPPS-NH2. In the present invention, it provides an enteric insulinotropic analogue having activity in each of a glucose-dependent insulinotropic polypeptide, a glucagon-like peptide-1, and a glucagon receptor, the polypeptide analogue can be used for treating and preventing metabolic disorders and other diseases including diabetes mellitus, obesity, metabolic syndromes and related diseases through various administration modes, and the polypeptide analogue can be used for treating and preventing metabolic disorders including diabetes mellitus, obesity, metabolic syndromes and related diseases through various administration modes.

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.