39 results about "Glucagon-like peptide 1 receptor" patented technology

The invention relates to application of a polypeptide compound having double agonist effects on a glucagon-like peptide-1 receptor and a glucagon receptor. The polypeptide compound has the characteristics of high enzymolysis stability, high bioactivity, no adverse reaction, etc., can alleviate abnormal rise in the levels of total cholesterol and triglyceride in blood induced by diabetes and high-meal diet, lowers the level of liver enzyme, improves liver damage and fibrosis stage and is applicable to prevention or treatment of diseases like non-alcoholic fatty liver diseases, hyperlipidemia and arteriosclerosis.

The present invention relates to a novel peptide showing more excellent activities on a glucagon like peptide-1 receptor and a glucagon receptor than native oxyntomodulin, and a composition for the prevention or treatment of obesity comprising the peptide as an active ingredient. Unlike native oxyntomodulin, the novel peptide of the present invention reduces food intake, suppresses gastric emptying, and facilitates lipolysis with reduced side-effects, and also shows excellent receptor-activating effects. Thus, it can be widely used in the treatment of obesity with safety and efficacy.

The invention is directed to a fusion protein comprising at least one FGF-21 (fibroblast growth factor-21) compound and at least one GLP-1R (glucagon-like peptide-1 receptor) agonist as well as to pharmaceutical compositions, medical uses and methods of treatment involving the fusion protein, particularly in the field of diabetes, dyslipidemia, obesity and / or adipositas.

Compounds that bind the glucagon-like peptide 1 receptor (GLP-1) receptor are provided including compounds which are modulators of the GLP-1 receptors and compounds which are capable of inducing a stabilizing effect on the receptor for use in structural analyses of the GLP-1 receptor. Methods of synthesis, methods of therapeutic and / or prophylactic use, and methods of use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor of such compounds are provided.

GLP-1 fragments and derivatives thereof are able to interact with and activate the GLP-1 receptor GLP-1 fragments and derivatives thereof are used either alone or in combination with other pharmaceuticals in the treatment of type 1 and type 2 diabetes and other pathologies that are known to benefit from activation of the glucagon-like peptide-1 receptor.

Compounds that bind the glucagon-like peptide 1 receptor (GLP-1) receptor are provided including compounds which are modulators of the GLP-1 receptors and compounds which are capable of inducing a stabilizing effect on the receptor for use in structural analyses of the GLP-1 receptor. Methods of synthesis, methods of therapeutic and / or prophylactic use, and methods of use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor of such compounds are provided.

Treatment of hyperinsulinemic hypoglycemia comprises administration of an effective amount of a glucagon-like peptide-1 receptor antagonist (GLP1RA) alone or in combination with an amylinomimetic agent or any anti-gastric emptying agent. Patients suffering from hyperinsulinemic hypoglycemia after bariatric surgery experience particular benefit, as there is no current method effective for their treatment. Prevention or reduction of acute adverse effects of postprandial hypoglycemia, such as palpitations, tremor, weakness, sweating, confusion, fatigue, blurred vision, seizures, or loss of consciousness, and prevention of chronic adverse effects of hyperinsulinemic hypoglycemia, such as cognitive impairment, can be achieved by treatment with GLP1RA.

Compositions and methods for treating hyperinsulinemic hypoglycemia, such as hyperinsulinemic hypoglycemia after bariatric surgery, are provided. In some embodiments, an effective amount of the glucagon-like peptide-1 receptor antagonist exendin(9-39) is subcutaneously administered twice per day.

The invention provides substituted cyclic compound presented with general formula Iand II, method for preparing the same and application of preventing or treating metabolic disorder disease (including diabetes, insuline resistance and adiposis, and etc.) As modifier for glucagons-1 acceptor.

The invention provides a drug for treating hepatocellular carcinoma. The drug comprises a glucagon-like peptide-1 receptor stimulant and / or a dipeptidyl peptidase 4 inhibitor. The invention further provides application of the glucagon-like peptide-1 receptor stimulant and / or dipeptidyl peptidase 4 inhibitor to preparation of a drug for preventing or treating hepatocellular carcinoma, to preparation of a drug for liver function recovery after liver transplantation, and to preparation of a drug for preventing liver cancer relapse after liver transplantation. The glucagon-like peptide-1 receptor stimulant and / or dipeptidyl peptidase 4 inhibitor generates a differential effect in a tissue specificity way, so as to inhibit cancer cell proliferation and promote cancer cell apoptosis, meanwhile, liver cells are protected against apoptosis, so that obesity-dependent liver cancer or non-dependent liver cancer can be treated or weakened.

Jasminoidin serving as a GLP-1 (Glucagon-Like Peptide-1) receptor stimulating agent plays a role in protecting pancreatic beta cells. The invention belongs to the field of combination of traditional Chinese pharmacology, endocrinology and molecular pharmacology, and particularly relates to specific activation of a glucagon-like peptide-1 receptor (GLP-1R) signal channel through jasminoidin for prompting the survival of pancreatic beta cells and realizing a hypoglycemic effect. Mouse primary pancreatic beta cells are cultured by adopting a hypoglycemic Chinese medicinal jasminoidin active ingredient, so that beta cell proliferation can be promoted remarkably, apoptosis is inhibited, and beta apoptosis rate in a high-sugar or inflammatory factor environment is lowered simultaneously. Through a siRNA (small interfering Ribonucleic Acid) experiment, the expression of the GLP-1R in beta cells is lowered, and the protecting effect of jasminoidin on beta cells is inhibited. The invention discloses the effect of jasminoidin serving as a GLP-1 stimulating agent for protecting pancreatic cells by specifically activating a GLP-1R channel, explains the molecular pharmacological mechanism of jasminoidin on the treatment of diabetes mellitus, and lays a theoretical foundation for treating diabetes mellitus with the traditional Chinese medicine.

The present invention provides uses of a glucagon-like peptide 1 receptor agonist in combination with metformin. Uses include treating type 2 diabetes, lowering blood glucose, and improving the therapeutic effectiveness of metformin. The invention also provides pharmaceutical compositions that comprise a GLP1R agonist and metformin.

The invention provides a compound with substituted cyclobutane structure represented as formula I or II, a relative preparation method, and an application of being glucagon-like peptide-1 receptor modulator to prevent and / or treat metabolic disorder (as diabetes, insulin resistance and obesity or the like), cardiovascular disease and neurodegenerative disease (as Alzheimer's) or the like.

The invention provides a substituted five-member heterocyclic compound the formula of which is as follows and salt, ester, a solvate, a metal complex, or a prodrug with the same pharmacological effect thereof and an application as a glucagon-like peptide-1 receptor regulation agent being used for preventing and / or treating the diseases such as metabolic disorders (including but not limited to sugar diabetes, insulin resistance and adiposis), cardiovascular diseases, neurodegenerative diseases ( such as: Alzheimer's Disease, AD, also named: Alzheimer's dementia), etc.

The invention provides a substitute five membered heterocyclic compound represented by the following formula, and salt, ester, solvate and metal composition which are all accepted by pharmacy or a prodrug having the same biological activity. The invention also provides a purpose of the compound as a glucagon-like peptide-1 receptor (GLP-1R) signal transduction positive modulator and an application for preventing and / or curing metabolic diseases (including but not being limited to type-2 diabetes, insulin resistance and adiposity, and the like), angiocardiopathy and neurodegenerative diseases (such as Alzheimer's disease, AD) also called presenile dementia, and the like.

The present invention provides the glucagon-like peptide-1 receptor agonists. It is indicated that the agonists have good binding capability to glucagon-like peptide-1 receptor by pharmacological tests. The present invention also provides the preparation of the agonists.

The invention relates to uses of polypeptide compounds having dual target agonist effect on glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR). Characterized by high enzymolysis stability, high biological activity and no adverse reaction, the polypeptide compounds are capable of reducing abnormal increase of triglycerides and total cholesterol in blood induced by diabetes mellitus and high fat diet, reducing liver enzyme level, reducing liver injury and fibrosis stage, and preventing or treating non-alcoholic fatty liver diseases (NAFLDs), hyperlipemia and arteriosclerosis.

Nanocapsule systems of at least one active pharmaceutical ingredient selected from the group consisting of at least one insulin, insulin analogue, insulin derivative, glucagon-like peptide-1 receptor agonist (GLP1 R agonist) and / or dual GLP-1 receptor / glucagon receptor agonist and / or or any combination thereof are disclosed.

The invention provides a compound with a substituted four-membered ring structure represented as formula I or II, relative pharmacy acceptable salt, ester, solvent and metal complex, or prodrug with same pharmacologia function, and ra elative application of being glucagon-like peptide-1 receptor modulator to prevent and / or treat metabolic disorder (as diabetes, insulin resistance and obesity or the like), cardiovascular disease and neurodegenerative disease (as Alzheimer's) or the like.

The invention discloses <68>Ga marked NOTA-MAL-Cys<39>-exendin-4 compound as well as a preparation method and application thereof. The <68>Ga-NOTA-MAL-Cys<39>-exendin-4 is prepared from <68>Ga marked precursor compound of NOTA-MAL-Cys<39>-exendin-4. Synthesizing time of the <68>Ga-NOTA-MAL-Cys<39>-exendin-4 disclosed by the invention is about 25min, a labeling yield is as high as 80% or more, HPLC determination shows that a product radiochemical purity is larger than 98%, and the marked product of the <68>Ga-NOTA-MAL-Cys<39>-exendin-4 can be specifically combined with glucagon-like peptide-1 receptor (GLP-1R), is a GLP-1 receptor photographic developer having potential and is suitable for being applied to clinical insulinoma diagnosis.

The invention relates to dual-target polypeptide compounds and use of the dual-target polypeptide compound in preparation of a drug for treating diabetes and diseases characterized by the same. The invention belongs to the field of biomedical chemistry, and relates to the dual target polypeptide compounds glucagon-like peptide-1 receptor(GLP-1R) and a glucagon receptor (GCGR) having the agonisticeffect at the same time. The dual-target agonist-polypeptide compound provided by the invention can simultaneously agonize both GLP-1R and GCGR membrane receptors, has the ability to effectively regulate collective glucose homeostasis and energy metabolism, and can significantly lower blood glucose concentration. The polypeptide compound provided by the invention has high biological activity and low side effects; exhibits remarkable stability in pharmacological experiments of drugs; is subjected to amplification production , has low cost, and has potential for preparing the drug for treating diabetes.

The invention provides a cell line for scanning peptide and non-peptide GLP-1 (Glucagon-like Peptide-1) analogues as well as a preparation method and application thereof and belongs to the technical field of high-flux screening and detection of medicines. The invention relates to the detection device for stably expressing the establishment of a fluorescence labeling human glucagon-like peptide-1 receptor (GLP-1R) protein cell line GLP-1R / U2OS, forming fluorescence spots in cells after the GLP-1R / U2OS cell line is stimulated by the GLP-1 analogue Exendin-4 and determining the bioactivity of the GLP-1 analogues by observing form changes through utilizing a high-content system. The detection method provided by the invention is easily standardized, has good repeatability, has the characteristics of GLP-1 receptor specificity, low cost, accuracy and convenience and has a good application prospect.

Compounds represented by formula (I):wherein each symbol is as defined in the present specification, or a salt thereof are useful for the prophylaxis or treatment of diabetes and obesity, and diseases related thereto.

The present invention relates to combinations, pharmaceutical compositions and fusion molecules comprising an FGF21 (fibroblast growth factor 21) compound and a GLP-1R (glucagon-like peptide-1 receptor) agonist with optimized GLP-1R agonist / FGF21 compound activity ratio. It further relates to their use as medicaments, in particular for the treatment of obesity, being overweight, metabolic syndrome, diabetes mellitus, diabetic retinopathy, hyperglycemia, dyslipidemia, Non-Alcoholic SteatoHepatitis (NASH) and / or atherosclerosis.

The present invention provides the glucagon-like peptide-1 receptor agonists. It is indicated that the agonists have good binding capability to glucagon-like peptide-1 receptor by pharmacological tests. The present invention also provides the preparation of the agonists.

A monomeric peptide that functions as an agonist for the glucagon receptor (GluR), the glucagon-like peptide 1 receptor (GLP1-R) and neuropeptide Y2 receptor (NPY2-R). The peptide thus targets three of the receptors involved glucoregulation and appetite regulation to more efficiently and completely facilitate weight loss in, among others, type II diabetic patients while also being capable of stimulating a reduction in appetite to complement the weight loss results.

Provided are a pharmaceutical composition for preventing or treating muscle atrophy or sarcopenia including glucagon-like peptide-1 (GLP-1), a GLP-1 fragment, a GLP-1 secretion enhancer, a GLP-1 degradation inhibitor, a GLP-1 receptor (GLP-1R) agonist, or exendin-4, and a method of treating muscle atrophy or sarcopenia by using the pharmaceutical composition. When the pharmaceutical composition for preventing or treating muscle atrophy or sarcopenia provided in the present invention is administered to a subject having sarcopenia or muscle atrophy, reduced body weight, skeletal muscle mass, and grip strength, which are caused by sarcopenia or muscle atrophy, and expression levels of genes involved in muscle production may be restored to normal states, and therefore, the composition may be widely applied to the development of effective therapeutic agents for sarcopenia or muscle atrophy.

A method for the avoidance of side effects associated with glucagon-like peptide-1 receptor (GLP-1R) agonists through vitamin B12 conjugation prior to administration. Vitamin B12 may be bound to a GLP-1R agonist, such as exendin-4 (Ex4), to provide enhanced proteolytic stability while retaining GLP-1R agonism. The conjugate (B12-Ex4) also improves glucose tolerance without producing anorexia and malaise. A GLP-1R agonist that is resistant to DPP-IV degradation and does not penetrate readily into the CNS, but retains the enhanced pharmacokinetic and pharmacodynamic profile on pancreatic β-cells provide a pharmacological tool for glycemic control in type 2 diabetes mellitus (T2DM) patients without eliciting unwanted hypophagia and nausea.

Methods for inhibiting platelet aggregation using glucagon-like peptide-1 receptor (GLP-1R) agonists are disclosed. GLP-1 receptors are demonstrated to be expressed in platelets and / or megakaryocytes. Activation of GLP-1 receptors by GLP-1 agonists, such as GLP-1 and exendin-4, inhibited thrombin-induced platelet aggregation.

The present invention provides a novel bifunctional polypeptide-derived compound and a preparation and an application thereof. Specifically, the present invention discloses the whole new polypeptide-derived compound having a structure shown in a formula A, and a use thereof as a dipeptidyl peptidase-4 (DPP-4) inhibitor and a glucagon-like peptide 1 receptor (GLP1R) activator. The polypeptide exhibits good DPP-4 inhibiting activity and GLP1R activating activity, and has an application value for treating type 2 diabetes.