48 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.

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.

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.

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.

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 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 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 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.

It relates to 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, obesity and T2DM.

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. In addition, these properties also enable GPCR agonist fusion proteins to transport across the blood-brain barrier, and thus allow for the treatment of neurological disorders.

The present invention relates to a use of a novel triple activator, having activity in all of GLP-1, GIP, and a glucagon receptor, for preventing or treating cardiovascular diseases.

To provide a treatment option that provides an extended duration of therapeutic action while reducing dosing frequency in the treatment of diabetes.SOLUTION: Provided are compounds comprising a therapeutic polypeptide Fc conjugate having activity at one or more of the GIP, GLP-1, and glucagon receptors. These compounds provide activity at one or more of these receptors and have structural features that extend the duration of action. Also provided are methods for treating diseases and / or conditions such as obesity, chronic weight management, and type 2 diabetes.SELECTED DRAWING: None

Provided herein are peptides and peptide conjugates having activity as triple agonists of the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide 1 (GLP-1) receptor, and the glucagon (GCG) receptor. The peptide conjugates provided herein are cross-linked via a half-life extending staple. The peptides and peptide conjugates may be used for blood glucose management and treating conditions such as diabetes mellitus, obesity, dyslipidemia, metabolic syndrome, and metabolic dysfunction-associated steatohepatitis (MASH).

The present invention relates to a composition comprising insulin and a triple agonist having activity on the glucagon receptor, the GLP-1 receptor and the GIP receptor, and to a combination preparation comprising the composition.

The present invention relates to a method of treating and / or preventing a disease or disorder in a subject, the method comprising administering to the subject about 1 mg to about 15 mg of an amylin receptor (AMYR) agonist and about 0.1 mg to about 10 mg of a GLP-1 receptor (GLP-1R) agonist (e.g. a GLP-1R / glucagon receptor dual agonist). Also provided are corresponding compositions and kits.

To develop a stable liquid formulation of a persistent conjugate of a peptide active against all developed glucagon receptors, GLP-1 receptors, and GIP receptors, which can be stored for extended periods without concerns about viral contamination. [Solution] The present invention relates to a liquid formulation of a sustained-release conjugate of glucagon, GLP-1, and GIP triple-active compound, and a method for producing the same.

Described herein are compositions formulated for oral administration comprising luteolin, luteolin-7-0-β-D-glucoside, or mixtures thereof, wherein luteolin, luteolin-7-0-β-D-glucoside, or mixtures thereof activate all of the glucagon-like peptide 1 receptor (GLP-1R), glucose-dependent insulinotropic peptide receptor (GIPR), and glucagon receptor (GCG). Luteolin and luteolin-7-0-β-D-glucoside are triple agonists of GLP-1, GIPR, and GCGR. Further, described herein are methods of treating and / or preventing type 2 diabetes and obesity by administering the described compositions. Further, described herein are methods of activating all GLP-1R, GIPR, and GCGR comprising providing a composition comprising a triple agonist of all GLP-1R, GIPR, and GCGR, wherein the triple agonist is luteolin and / or luteolin-7-0-β-D-glucoside.