3006 results about "Agonist" patented technology

Disclosed are methods of improving treatment adherence and compliance after discontinuation of incretin-based therapies, such as GLP-1 and / or GIP agonists, using pharmacotherapies comprising the disclosed therapeutic compounds and combinations. In some aspects, methods include treatment of psychological factors affecting other medical conditions (PFAOMC) following the administration of incretin-based therapies to treat obesity or hyperglycemia, and related disorders. In some aspects, disclosed pharmacotherapies for use in the methods include agents that modulate monoaminergic neurotransmission, administered alone or together, such as in disclosed combinations having advantageous synergistic effects.

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 a preparation method of a GLP-1R agonist Orforglipron, which comprises the following reaction steps: carrying out four-step reaction on an oxopiperidine compound (1) and (4-fluoro-3, 5-dimethylphenyl) hydrazine (2) to obtain a compound 8, and carrying out seven-step reaction on 5-bromo-indolecarboxylic acid (9) to obtain a compound 17. Then, the compound 8 and a compound 17 are subjected to an acid amine condensation reaction, and Orforglipron (LY3502970) is obtained. The preparation method is relatively low in cost, easy to operate, relatively short in synthetic route and suitable for industrial production and application, and the total yield can reach 32%.

The invention belongs to the technical field of genetic engineering and biological medicine, and particularly discloses a cascade response type nano-particle with a microenvironment remodeling function and a preparation method and application of the cascade response type nano-particle. The nanoparticle provided by the invention adopts a bionic hybrid membrane engineering strategy: an inner core is formed by loading an exosome inhibitor on a nano material, and the surface is covalently coupled with M2 type macrophage specific targeting peptide; the outer layer coats a macrophage membrane and active oxygen response type liposome composite membrane layer through a co-extrusion technology, and is loaded with a TLR agonist. Animal experiments show that after being injected through caudal vein, the nano-particles are enriched at a tumor site in a targeted manner through homing receptors such as membrane surface integrin alpha4beta1 and the like, and outer membrane cracking is triggered in a high-ROS tumor microenvironment, so that space-time controlled release of a TLR agonist and targeted phagocytosis of an exosome inhibitor by macrophages guided by a targeted peptide are realized. The anti-tumor synergistic effect is achieved through multiple regulation and control mechanisms, and an effective treatment strategy is provided for tumor immunotherapy.

The present invention provides a compound as an APJ receptor agonist. The compound is a compound represented by formula (I), or an isotopic variant, tautomer, stereoisomer or pharmaceutically acceptable salt thereof. The present invention further provides a pharmaceutical composition comprising the compound, and a use thereof in the treatment or prevention of diseases associated with APJ.

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.

Methods for enhancing weight loss, or preventing or treating obesity or other conditions related thereto, such as diabetes, involve administering a GLP-1 agonist together with, or prior to, administering a mitochondrial uncoupler. Use of the uncoupler increases weight loss and enhances treatment of obesity and obesity-related medical conditions, such as by preventing weight regain after cessation of administration of the GLP-1 agonist.

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.

Disclosed herein are heterocyclic compounds that activate GLP-1R pathways. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the GLP-1R agonists are disclosed, alone or in combination with other therapeutic agents, for the treatment of diabetes, obesity, and other diseases or conditions dependent on GLP-1R pathways.

The present invention provides a method for inducing fat accumulation in a cell of a fish, including contacting a cell obtained or derived from a fish with an effective amount of a composition including: (i) a fat accumulation inducing agent; and (ii) a carrier, wherein the fat accumulation inducing agent consists essentially of a free fatty acid and a peroxisome proliferator-activated receptor gamma (PPARy) agonist. Further provided are a cultured fish cell including an increased amount of a PUFA and a reduced amount of MUFA, compared to a control fish cell, and an edible composition including the same.

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 present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.

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 present invention belongs to the technical field of cancer immunotherapy, and particularly relates to a cholesterol-modified cationic liposome tumor vaccine, a preparation method therefor, and use thereof. In order to solve the problems of poor targeting and strong side effects of TLR agonists in anti-tumor treatment, the present invention provides a cationic liposome prepared from a cholesterol-modified 1V209 molecule, a cationic lipid component, cholesterol, and DSPE-PEG2000, and then the cationic liposome and ovalbumin 5 form the tumor vaccine by electrostatic adsorption. Animal experiments show that the vaccine can induce antigen-specific CD8+ T cells, activate lymphocytes, and generate stronger antigen cross-presentation, more memory T cells, antibodies, and cytokines. Prophylactic inoculation with the vaccine can significantly delay the progression of mouse melanoma and lymphoma and prolong the survival of mice. The combination use of the vaccine and a PD-1 checkpoint inhibitor can further enhance the anti-tumor effect. Therefore, the vaccine is a promising cancer vaccine.

Provided are a GLP1 analogue and GLP1 / GIP receptor co-agonist analogues, a fusion protein comprising the GLP1 analogue or the GLP1 / GIP receptor co-agonist analogue, and methods of use thereof. In various embodiments, the fusion protein comprises the GLP1 analogue or the GLP1 / GIP receptor co-agonist analogue fused to a protecting antibody or further fused to a stabilizing domain. In some embodiments, the fusion proteins are useful for treating or ameliorating a symptom or indication of a disorder such as obesity and diabetes.

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.