2552 results about "Agonist" patented technology

A class of compounds and the use thereof in a drug. Specifically, the present invention relates to a class of new compounds, a pharmaceutical composition containing the compounds, a method for preparing the compounds, and the use of the compounds or the pharmaceutical composition in the preparation of a drug for treating GLP-1 receptor agonist-mediated diseases and / or disorders, particularly the use in the preparation of a drug for treating diabetes, non-alcoholic fatty liver disease, obesity, myocardial infarction, heart failure, diabetic nephropathy, Parkinson's disease and Alzheimer's disease.

The invention discloses an APJ receptor agonist and application thereof in medicine. In particular, the present invention discloses a compound of formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the same, and a use of the compound as an Apelin receptor agonist in the preparation of drugs for treating related diseases, each group in the formula (I) being as defined in the specification.

The invention provides a compound of a GLP-1R agonist or modulator with a structure as shown in a formula (I).

Disclosed herein are methods for treating a subject with T2DM, obesity, or overweight with at least one weight related comorbidity using a glucagon-like peptide-1 (GLP-1) receptor non-peptide agonist (NPA) compound selected from Compound 1, Compound 1a, Compound 2, Compound 3, pharmaceutically acceptable salts thereof, and hydrates of the compounds and pharmaceutically acceptable salts, by oral administration to maintain body weight loss or reduced HbA1c levels resulting from a prior treatment with a GLP-1 RA. Also disclosed herein are uses of a GLP-1 receptor NPA compound for the manufacture of a medicament for treating a subject with T2DM, obesity, or overweight with at least one weight related comorbidity to maintain body weight loss or reduced HbA1c levels resulting from a prior treatment with a GLP-1 RA.

The present disclosure is related to dual payload immunostimulatory antibody drug conjugates comprising at least STING agonist and at least one cytotoxic agent, pharmaceutical compositions thereof, and the use of the dual payload immunostimulatory antibody drug conjugates and compositions thereof for the treatment of diseases and disorders, including proliferative diseases.

The present invention addresses the problem of providing a novel compound that has an OX2R agonist activity.　The present invention relates to a substituted sulfonamide compound which is represented by formula (I) or a pharmacologically acceptable salt thereof. A compound according to the present invention, or a pharmacologically acceptable salt thereof, has an agonist activity against OX2R, and is useful as, for example, a therapeutic agent for sleep disorders associated with OX2R (for example, narcolepsy, idiopathic hypersomnia, Kleine-Levin syndrome, hypersomnia associated with a physical disease, hypersomnia associated with a mental disease, hypersomnia associated with a drug or a substance, circadian rhythm sleep-wake disorders, insufficient sleep syndrome, and extended sleep).

Provided are: a method for producing an organoid, the method comprising a step for culturing somatic stem cells in a culture medium containing an agonist of the interferon-γ receptor; and a culture medium for producing an organoid, the culture medium containing an agonist of the interferon-γ receptor.

The present disclosure relates to IL12 receptor agonists with improved therapeutic profiles.

The present invention relates to a compound having a structure represented by formula (I) and having GLP-1 receptor agonistic activity; and the use of said compound and a pharmaceutically acceptable salt, stereoisomer, solvate, or hydrate thereof in the preparation of a GLP-1 receptor agonist and in the preparation of a drug for treating and / or preventing metabolic diseases.

The invention belongs to the field of biological medicines, and particularly discloses application of a Ptprj agonist GJ103 in preparation of a medicine for treating acute kidney injury (AKI) induced by cisplatin. In-vivo and in-vitro experiments prove that the GJ103, by activating Ptprj, can significantly down-regulate expression of pro-apoptotic protein Bax and Cleved Caspase-3, up-regulate anti-apoptotic protein Bcl2 and reduce infiltration of inflammatory factors TNF-alpha and IL-6, so that apoptosis and inflammatory response of renal tubular epithelial cells are relieved. In in-vivo experiments, GJ103 (20-40mg / kg / day) can reduce serum creatinine and urea nitrogen levels of cis-platinum model mice and improve pathological injuries such as renal tubule dilatation; in in-vitro experiments, 20-40 [mu] M of GJ103 can inhibit apoptosis of renal tubular epithelial cells and reduce expression of renal injury markers NGAL and Kim-1. The pharmaceutical composition contains GJ103 and a pharmaceutical carrier, the preparation form can be a 4mg / mL injection (the purity is greater than or equal to 99.46%) or an oral preparation, and a new strategy is provided for clinical treatment of cisplatin renal toxicity.

The application provides a Huangdache oligosaccharide with GLP-1 agonist activity and application thereof, and belongs to the technical field of medicines. 3 The oligosaccharide component ELYP-3 has a molecular weight of 3.2*10 3 Da, and the molar ratio of monosaccharides is rhamnose:galacturonic acid:glucose:galactose:arabinose = 1:32.42:45.37:9.11:6.54. The Huangdache oligosaccharide fragment obtained by glycosidase degradation has significant hypoglycemic and weight loss activities, the preparation process is simple, specific and green, and provides scientific basis and theoretical support for the development of natural GLP-1 agonists. Meanwhile, the functional oligosaccharide provides a wide application prospect for the development of medicines with blood glucose regulation.

The invention discloses a novel herpes zoster vaccine composition and a preparation method, and belongs to the technical field of vaccines. The novel herpes zoster vaccine composition comprises gE protein and an adjuvant, the adjuvant is selected from at least one of an aluminum salt adjuvant, a saponin adjuvant, a TLR pathway agonist, an STING pathway agonist, an emulsion adjuvant and a liposome adjuvant. The invention also provides a preparation method of the composition. Compared with the prior art, the gE protein prepared by the method disclosed by the invention has the advantages that a protective matrix is jointly constructed by saccharides capable of forming a glassy state and a buffer system, and conformation is fixed through hydrogen bond replacement and vitrification in freezing and drying processes, so that interface-induced folding and aggregation are reduced; a small amount of surfactant weakens air-liquid and solid-liquid interfacial tension, terminal low-adsorption filtration reduces non-specific adsorption loss, and the monomer state and immunogenicity are maintained after redissolution.

Embodiments disclosed herein include methods and systems for managing outcomes for weight-loss GLP-1 receptor agonist therapies using biochemical data-trained models and / or other patient centric analysis. In some embodiments, one or more biomarkers or other patient data are employed for training AI / ML or other computational models and / or as inputs to AI / ML or other computational models to evaluate patient response to GLP-1 receptor agonist therapy. For example, the computational models may be configured to perform classifications with respect to success of GLP-1 receptor agonist therapy and / or adverse effects during GLP-1 receptor agonist therapy.

The present invention relates to the use of a pharmaceutical composition in the form of extended-release tablets containing Pirfenidone for treating NAFLD / NASH and advanced liver fibrosis by decreased serum cholesterol and triglycerides as well as reducing the content of hepatic fat accumulation, both in the form of macrosteatosis and microsteatosis. Additionally, its use as an agonist for PPARgamma (peroxisome proliferation receptor activated gamma), PPARalpha (peroxisome proliferation receptor activated alpha), LXR and CPT1, key molecules in the metabolism of fatty degradation and inflammation of the liver. In addition, another use is the induction of decreased expression of NFKB master gene, transcriptional inducer of hepatic inflammatory process factor. All of these events results in the reversal of NAFLD / NASH and advanced liver fibrosis.

The invention provides a lipidosome STING agonist delivery system based on a PD-L1 antibody as well as a preparation method and application of the lipidosome STING agonist delivery system, and belongs to the technical field of medical biology. Preparing lipidosome by adopting an ethanol injection method and an ammonium sulfate gradient technology; the PD-L1 antibody and the STING agonist can be loaded at the same time; the liposome is prepared by adopting an ethanol injection method and an ammonium sulfate gradient technology, and the STING agonist can be wrapped in the liposome in an active drug loading manner; dSPE-PEG2000-NHS and a PD-L1 antibody are mixed and incubated according to a specific proportion by utilizing a post-insertion method to form an antibody conjugated micelle, and the antibody conjugated micelle is fused with a blank liposome to realize antibody modification; secondly, the nano-liposome has good drug carrier characteristics and can effectively protect the loaded drug, reduce the risk of enzymolysis of the drug and improve the stability of the drug in vivo, so that the liposome drug delivery system simultaneously loading the nano-liposome and the nano-liposome is successfully prepared.

The invention belongs to the field of medicines, and particularly relates to application of a new target NCSTN for regulating and controlling bone metabolism and an agonist of the new target NCSTN in preparation of a medicine for preventing or treating osteoporosis. The invention aims to provide a new target NCSTN for regulating and controlling bone metabolism and application of the new target NCSTN in promoting osteogenic activity, inhibiting osteoclast activity and treating osteoporosis. According to the invention, the mechanism of the NCSTN agonist for treating osteoporosis is found for the first time, and the NCSTN agonist has the effects of inhibiting osteoclast maturation and differentiation and promoting osteoblast bone formation function. The mechanism is greatly different from the previously reported mechanism of singly inhibiting bone resorption or singly promoting bone formation, and the osteoporosis treatment which simultaneously acts on bone resorption and bone formation can greatly reduce the adverse reaction of the body to the medicine.

The invention discloses a compound as shown in a formula (I), and / or pharmaceutically acceptable salts thereof, and / or a raceme mixture, a hydrate, a solvate, a prodrug, an enantiomer, a diastereoisomer and a tautomer thereof, and belongs to the technical field of medicines. The invention also discloses a pharmaceutical composition containing the compound as shown in the formula (I), and the compound as shown in the formula (I) and / or a pharmaceutically acceptable salt thereof, and / or a racemic mixture, a hydrate, a solvate, a prodrug, an enantiomer, a diastereoisomer and a tautomer thereof, and / or the pharmaceutical composition, a pharmaceutically acceptable salt thereof, and / or a racemic mixture, a hydrate, a solvate, a prodrug, an enantiomer, a diastereoisomer and a tautomer thereof. The invention further discloses application of the cGAS agonist in preparation of the cGAS agonist and a medicament for treating diseases responding to activation of the cGAS-STING signal channel.

The invention relates to the field of disease animal model construction, and particularly discloses a postmenopausal osteoporosis and knee osteoarthritis co-disease animal model construction method which comprises the following steps: selecting a female animal as an experimental subject; the selected female animals are injected with a GnRH agonist, meanwhile, low-calcium feed feeding and oxidative stress stimulation are conducted, and feeding is conducted for a preset time; detecting bone mineral density and bone trabecula parameters of the fed female animals, and screening qualified female animals meeting set standards; performing meniscus tearing operation on the qualified female animal, and implanting sustained release microspheres loaded with inflammatory factors at the torn part during the operation; carrying out weight-bearing training on the female animal after the operation, and continuing for a set time length; and performing health detection on the female animals at different time points. According to the method, through multi-factor collaborative induction of the PMOP, minimally invasive construction of the KOA and multi-dimensional health detection, accurate simulation of a co-disease pathological process and clinical characteristics is realized, and the authenticity and stability of the model are improved.

The invention belongs to the technical field of medicines, and provides a novel method for overcoming multidrug resistance of tumors based on innate immune regulation. The invention relates to an application of an agonist of an innate immune STING pathway and an ENPP1 inhibitor in overcoming multidrug resistance of tumors and enhancing an anti-tumor curative effect. The STING agonist or the ENPP1 inhibitor is combined with an anti-tumor chemical drug for application, so that the effects of overcoming the multi-drug resistance of chemotherapeutic drugs and enhancing the anti-tumor curative effect are achieved. The STING agonist / or ENPP1 inhibitor has the effect of reversing multidrug resistance of tumors, and can enhance the sensitivity of cancer cells to chemotherapeutic drugs and monoclonal antibody drugs, so that the curative effect of antitumor drugs is enhanced, and the STING agonist / or ENPP1 inhibitor is expected to be developed into a novel reversal agent drug for multidrug resistance tumors. The novel anti-multidrug resistance strategy provides a new thought for drug design and cancer treatment, and has a great application prospect in clinical treatment of cancers.

The invention provides a synthesis method of a selective THRbeta agonist key intermediate compound as shown in the formula (II). The synthesis method has the advantages of cheap and easily available raw materials, simple and efficient process, no need of SFC chiral resolution, high yield, controllable quality and cost, and huge industrialization prospect.

The present invention provides compositions comprising one or more ACAT inhibitors and one or more GLP-1 receptor agonists (GLP-1 RAs). The combination therapy reduces side effects associated with high-dose GLP-1 RA monotherapy and provides durable management of weight loss by suppressing rebound of body weight, blood glucose, and cholesterol levels after treatment.

The present invention relates to combination therapies employing tumor targeted anti-CEA / CD3 bispecific antibodies and / or agents blocking PD-L1 / PD-1 interaction in combination with 4-1BB (CD137) agonists, in particular 4-1BBL trimer containing antigen binding molecules that also target FAP, the use of these combination therapies for the treatment of cancer and methods of using the combination therapies.

The present application relates to heterobicyclic compounds having glucagon-like peptide receptor (GLP-1R) agonist activity, processes for their preparation, pharmaceutical compositions comprising them and their use as GLP-1R agonists or for the treatment or prophylaxis of GLP-1R associated diseases or disorders. In particular, the compounds of the present application are useful for body weight management, for lowering blood sugar and / or for the treatment or prevention of diabetes, diabetic complications, obesity, overweight, dyslipidemia, fatty liver diseases (e.g., non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)), metabolic diseases, cardiovascular diseases, nervous system disorders, mental disorders, kidney diseases, etc. , gastrointestinal diseases, autoimmune diseases, inflammatory diseases, lung diseases, hypothalamic-pituitary-gonad axis related diseases or disorders, cancers and the like.

Described herein are pharmaceutical formulations of a farnesoid X receptor agonist, 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate, and methods of using such pharmaceutical formulations in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.

The present invention relates to a pharmaceutical composition for oral administration comprising a GLP receptor agonist or a pharmaceutically acceptable salt or derivative thereof, one or more penetration enhancers, one or more mucous membrane adhesives, and one or more basifying agents. More preferably, the penetration enhancer is a penetration enhancer based on medium chain fatty acids.

Fusion molecules comprising an obesity-related peptide moiety, fused to a myostatin pathway inhibitor moiety are disclosed. Also disclosed are nucleic acids and expression vectors encoding, compositions comprising, and methods of using, the fusion molecules.

Methods and compositions comprising one or more dopamine neuronal activity enhancers (e.g., dopamine receptor agonists), pantethine and solubilized curcumin for use in treating NAFLD and NASH are provided.Methods and compositions comprising one or more dopamine neuronal activity enhancers (e.g., dopamine receptor agonists), pantethine and solubilized curcumin for use in treating NAFLD and NASH are provided.