64 results about "Receptor activation" patented technology

The present disclosure provides compounds, pharmaceutical compositions, and methods for treating a mental disorder in a subject, which may include administering to the subject a pharmaceutical composition including a therapeutically effective amount of a non-hallucinogenic 5-HT2A receptor agonist or a pharmaceutically acceptable salt thereof, thereby treating the mental health disorder in the subject.

Disclosed in the present application are a pyridopyrimidinone compound, and a preparation method therefor and the use thereof, wherein the pyridopyrimidinone compound, or a racemate, R-isomer, S-isomer, pharmaceutically acceptable salt thereof or a mixture thereof has a structure as shown in formula (I). The pyridopyrimidinone compound provided by the present application has an agonistic effect on an HsClpP protease, and can be used for treating diseases related to HsClpP receptor activation.

The invention discloses a method for multi-dimensionally researching synergistic effect among aromas based on human sense-olfaction receptors, which comprises the following steps: firstly, measuring threshold values and interaction effects of aroma substances by using sensory experiments so as to characterize olfaction perception interaction among aroma compounds; constructing an olfactory receptor in-vitro heterologous expression cell model and an olfactory receptor expression element; carrying out olfaction receptor expression and determination; and finally, determining the activation effect of the binary aroma system on the olfactory receptor, and comparing the activation effects of the single substance and the binary system on the receptor so as to research the interaction effect of the aroma compounds at the receptor level. The method is a brand-new method for researching interaction among fragrances from multiple angles based on human sense organs and olfactory receptors, combines the advantages of high integration of human sense organs and high sensitivity of olfactory receptors, makes up for the defect that the interaction of flavor substances can be researched only through human sense organ experiments in the prior art, is intuitive and reliable in shown result, and is suitable for large-scale popularization and application. The applicability is wide.

Provided are a method and system for predicting an activation potency of agonist molecules on G Protein-Coupled Receptors (GPCRs). The method includes: blindly speculating complex structures formed by binding of a ligand to an activated receptor structure and an inactivated receptor structure, respectively, via global molecular docking; extracting an initial path enabling an inactivated complex structure to be activated to an activated complex structure based on an enhanced sampling algorithm; searching for a minimum free energy path closest to the initial path by applying an automatic path optimization algorithm; calculating a free energy distribution curve along the minimum free energy path by employing umbrella sampling and determining an energy barrier height and a free energy difference before and after activation, thereby determining the activation potency of the ligand structure on the GPCRs.

Methods and materials for treating mammals having cardiovascular and / or metabolic disease are provided herein. For example, methods and materials for treating mammals having cardiovascular and / or metabolic disease by administering (a) an analog of a natriuretic peptide (NP), such as atrial natriuretic peptide (ANP) or dendroaspis natriuretic peptide (DNP), and (b) a glucagon-like peptide-1 (GLP-1) receptor / glucose-dependent insulinotropic polypeptide (GIP) receptor agonist are provided herein. The NP analogs used in the methods provided herein can be less than 20 amino acids in length and, in some cases, can have one or more variations in their ring portion (as compared to wild type ANP or DNP) that affect the potency of the analog in activating the particulate guanylyl cyclase (GC-A) receptor.

A fusion antibody and its application. The fusion antibody includes: a) IL-15; b) IL-15Ra; and c) an antibody targeting a therapeutically relevant cell surface antigen. The antibody includes a heavy chain variable region (VH), a heavy chain constant region (CH1), a light chain variable region (VL), and a light chain constant region (CL). IL-15 / IL-15Ra is located between the C-terminus of the heavy chain variable region VH and the N-terminus of the heavy chain constant region CH1, and between the C-terminus of the light chain variable region VL and the N-terminus of the light chain constant region CL. This fusion antibody prolongs its half-life and, utilizing its targeting properties, specifically reaches its target site to exert its effect, conferring IL-15 with unique cell targeting properties. It exerts its receptor activation effect only in an environment containing high receptor concentrations of IL-2βγ, thus reducing the systemic toxicity of the IL-15 / IL-15Ra complex.

The present invention relates to compounds of formula (I) as activators of glucagon-like peptide 1 (GLP1) receptor for the treatment of obesity, type 2 diabetes, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, one or more diabetic complications, diabetic nephropathy, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), hypertension, atherosclerosis, peripheral arterial disease, stroke, cardiomyopathy, atrial fibrillation, heart failure, coronary heart disease, and neuropathy.Preferred compounds are, for example, 2-((4-((S)-2-(4-chloro-2-fluorophenyl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-imidazole derivatives and similar compounds, such as C-1, C-2, C-3, C-4 and other compounds. [Formula 1] TIFF2024514826000258.tif26170 [chemical 2] TIFF2024514826000259.tif58170

The invention relates to application of an alpha1-adrenergic receptor antagonist, in particular to application of the alpha1-adrenergic receptor antagonist in treatment of alopecia, and the alopecia is alopecia caused by abnormal activation of an alpha1-adrenergic receptor. The alpha1-adrenergic receptor antagonist is combined with alpha1-adrenergic receptors of hair follicle cells to reduce the activation degree of the alpha1-adrenergic receptors, and can be used for performing targeted treatment on the alopecia in the rest period caused by abnormal activation of the alpha1-adrenergic receptors. A new action target is provided for treatment of alopecia in the stationary period.

The use of an active substance selected from an HCAR2 receptor activator, an HCAR3 receptor activator, an ester thereof, and a combination thereof in the preparation of a kit for detecting a neurological function state of a subject. The kit comprises several small chambers to accommodate different concentrations of aqueous solutions of the HCAR2 receptor activator or the HCAR3 receptor activator or the ester thereof. The kit can be used for effectively detecting the neural neurological state of the subject by means of evaluating the sensitivity of the subject to the HCAR2 receptor activator or the HCAR3 receptor activator or the ester thereof, and can be used for quickly obtaining a detection result by means of a few simple steps in a short time, so that real-time detections in multiple scenarios such as hospital wards, physical examination centers, and homes are achieved.

The invention relates to an application of an anti-CD73 monoclonal antibody combined with an Adora1 inhibitor in treatment of intestinal fibrosis. In the invention, the inventor finds that long-term WD generates GSDME-mediated pyroptosis by inducing intestinal epithelial cells and releases a large amount of intracellular molecules HMGB1 and ATP, the HMGB1 promotes CD39 + CD73 + CD8 + T cell amplification, the group of cells catalyzes extracellular ATP into Ado, and finally the Ado activates intestinal fibroblasts through a receptor Adara1 so as to participate in a complex intestinal fibrosis process. Based on this, the inventor finds that the CD-related intestinal fibrosis can be effectively improved by blocking the generation of intestinal adenosine or / and inhibiting the receptor of the intestinal adenosine, and a combined medicine, namely the anti-CD73 monoclonal antibody combined Adara1 inhibitor, is researched and developed, can be used for treating the CD-related intestinal fibrosis, and has important clinical application value.

A method for treating a patient suffering from a neuronal hypo-kinetic disease or a neuronal hyper-kinetic disease by modulating neuronal activity in the: internal globus pallidus (GPi), in the anterior motor thalamus and / or in the external globus pallidum (GPe) and / or in the subthalamic nucleus (STN) by utilizing suppressor and / or enhancer DREADDs is provided.

The application discloses a caviar polypeptide composition with enhanced immune function, a preparation method, application and preparation, belongs to the technical field of bioactive polypeptides, and comprises at least one polypeptide with an amino acid sequence of RWFPGKPLFWRA, FWKPLRGALFPW or KWRFPGALPWFA and a molecular weight of 1400-1550 Da. The preparation method comprises caviar protein extraction, complex enzymolysis, ultrafiltration separation, chromatography purification and solid-phase synthesis. Animal experiments prove that the polypeptide can significantly enhance cell immunity, humoral immunity, monocyte-macrophage function and NK cell activity, the mechanism is related to TLR2 / TLR4 receptor activation and NF-κB / MAPK signal pathways, the safety is good, and the polypeptide is suitable for development into an immune-enhancing health food or medicine.

Incorporation of lipids into a growing hair fibre is provided by a composition comprising at least one of: 1) 0.05 to 8 wt % of a lipid precursor selected from the group consisting of a fatty acid having a chain of 6 to 24 carbon atoms, an ester or an acylglycerol thereof and mixtures thereof; 2) 0.05 to 8.0% of a "gene activator material" that modulates the biosynthesis of lipids in the hair follicle or sebaceous gland, selected from a) at least one activator of a peroxisome proliferator-activated receptor (PPAR activator), b) at least one activator of a liver X receptor (LXR), and c) at least one activator of a retinoid X receptor (RXR); and 3) a fatty alcohol having a chain of 6 to 24 carbon atoms, preferably 8 to 20 carbon atoms, most preferably 10 to 18 carbon atoms; and mixtures thereof; and a cosmetically acceptable carrier.

The invention discloses a rapid detection kit for zebra fish cell capsaicin receptor activation. The rapid detection kit comprises an RNA purification column and an RNA collection tube or an RNA capture plate, washing buffer solutions A and B, a DNase I digestive juice, a 5x reverse transcription premix solution, a 2x SYBR Green qPCR premix solution, and specific primer dry powder or premix solution. The invention also discloses an application of the kit. The invention also discloses a method for screening a compound or a substance for regulating and controlling the activation of the capsaicin receptor of the zebra fish cell by using the kit. The novel primer sequence provided by the invention can accurately reflect the activation state of the TRPV1 pathway; a large number of samples can be processed in parallel through plate type design and reagent premixing, and the screening efficiency is improved by dozens of times; meanwhile, a receptor gene and a downstream early response gene are detected, so that an activation event can be confirmed, indirect evidence of pathway activity can be provided, and the result is more convincing.

The present invention provides the use of Caspase8 in the preparation of a medicament for non-alcoholic fatty liver disease. Overexpression of Caspase8 inhibits the development of non-alcoholic fatty liver disease. The present invention identifies a specific role of Caspase8 in non-alcoholic fatty liver disease: decreased Caspase8 expression in hepatic macrophages activates the Cflip / ELK4 / Psap signaling pathway, leading to macrophage polarization toward the M1 type. This, in turn, activates the Rac1 / cdc42 / JNK signaling pathway within hepatocytes through the Gpr37I1 receptor on the hepatocyte surface, leading to increased lipid deposition in hepatocytes. Caspase8 or its small molecule analogs may offer hope for the treatment of steatohepatitis.

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt thereof, e.g., in the treatment of a mental health disease or disorder.

Described herein are compositions, methods, and systems for modulating Notch receptor activation. Aspects of the invention relate to synthetic proteins comprising at least a mutant Notch NRR (Negative Regulatory Region). Another aspect of the invention relates to a protease-dependent synthetic protein. Engineered cells comprising the synthetic protein are additionally described herein.

A fusion antibody and a use thereof. The fusion antibody comprises: a) IL-15; b) IL-15Ra; and c) an antibody for targeted therapy against associated cell surface antigens, wherein the antibody comprises a heavy chain variable region VH, a heavy chain constant region CH1, a light chain variable region VL and a light chain constant region CL; IL-15 / IL-15Ra is located between a C terminal of the heavy chain variable region VH of the antibody and a N terminal of the heavy chain constant region CH1 of the antibody, and IL-15 / IL-15Ra is located between a C terminal of the light chain variable region VL of the antibody and a N terminal of the light chain constant region CL of the antibody. The fusion antibody can prolong a half-life period thereof and can use the targeting property of the antibody to specifically reach the site of action to exert the effect thereof, conferring specific cell targeting to IL-15. IL-15 can only exert the receptor activation effect thereof in an environment with high receptor concentrations of IL-2βγ, thereby reducing the systemic toxicity of an IL-15 / IL-15Ra complex.

The invention relates to a method for determining the ability of a molecule to modulate the activation of a G protein-coupled receptor (GPCR), said method comprising the following steps:a) introducing, in a first container:a membrane preparation bearing one or more GPCRs and one or more alpha G-proteins,a source of nonhydrolyzable or slowly hydrolyzable GTP labeled with a first member of a pair of RET partners,a ligand of the alpha subunit of a G protein (alpha G-protein) labeled with a second member of the pair of RET partners, said ligand being capable of binding to the full alpha G-protein bound to the nonhydrolyzable or slowly hydrolyzable GTP labeled with the first member of a pair of RET partners,optionally a GPCR agonist;b) measuring the RET signal emitted in the first container;c) introducing (i) in a second container, the same reagents as in step a) and the molecule to be assayed or (ii) in the first container, the molecule to be assayed;d) measuring the RET signal emitted in the second container or in the first container obtained in step c);e) comparing the signals obtained in steps b) and d), a modulation of the signal obtained in step d) relative to that obtained in step b) indicating that the molecule to be tested is capable of modulating the activation of the GPCR.

Compounds are provided having the structure of Formula (I): (Formula (I)) or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof, wherein R is as defined herein. Such compounds serve as modulators of the sphingosine-1-phosphate receptor, and have utility for treatment of a malcondition for which activation of this receptor is medically indicated.

1,1'-Biphenyl-4-yl-(het)arylimino-λ6-sulfanone compounds are 5-HT2A receptor activators, and these compounds and their pharmaceutical compositions are useful for the treatment of neurological or psychiatric disorders.

The invention relates to the technical field of biology, and particularly discloses application of macrophages in improving immunotherapy stomach cancer. The synergistic effect of CLEC2D + macrophages and a CD161 receptor in gastric cancer immune escape is focused for the first time, the single attention on macrophage M1 / M2 polarization and T cell checkpoint molecules in traditional research is broken through, a new T cell depletion mechanism driven by direct interaction of myeloid cells and lymphocytes is disclosed, and supplement is provided for the tumor immune escape theory; a novel blocking agent (such as a CD161 targeting antibody and a small molecule inhibitor) is developed on the basis of a mechanism of activating and mediating T cell depletion by a CD161 receptor, a basic mechanism research is directly converted into an innovative treatment scheme, and a differentiated strategy is provided for gastric cancer immunotherapy in combination with an existing PD-1 / PD-L1 inhibitor.

Use of NADPH in the preparation of a drug for treating major depression, bipolar disorder, post-stroke depression or neuroinflammation, and use of NADPH or a pharmaceutically acceptable salt thereof in the preparation of a P2X7 receptor antagonist. Research finds that NADPH inhibits the rise of an inward current in microglia caused by ATP-induced calcium influx and P2X7 receptor activation. It is indicated that NADPH can inhibit ATP-induced P2X7R activation and inflammasome activation and it is shown that NADPH can be used as a P2X7 receptor inhibitor, and can be further used for preventing or treating diseases caused by P2X7 receptor activation and inflammasome activation, wherein these diseases comprise major depression, bipolar disorder, post-stroke depression or neuroinflammation-related diseases.

The invention relates to a kit and a system for detecting a neurological function state of a subject. The kit comprises a plurality of small chambers for containing different concentrations of an HCAR2 receptor activator or an HCAR3 receptor activator or an ester aqueous solution thereof. The kit provided by the invention can be used for effectively detecting the neurological function state of a subject by evaluating the sensitivity degree of the subject to the HDAR2 receptor activator or the HDAR3 receptor activator or the ester thereof. The system disclosed by the invention can be used for quickly obtaining a detection result through several simple steps of operation in a short time, realizes multi-scene real-time detection in a ward, a physical examination center, a home and the like, and is an objective, convenient and effective biological detection means for detecting four nerve function states of a subject.

This invention belongs to the field of pharmaceutical technology, specifically relating to the application of N-methyltyramine in the preparation of drugs for improving anger and irritability. The CAS number of the N-methyltyramine (NMT) is 370-98-9. Experimental results show that NMT can directly target and positively regulate the γ-aminobutyric acid type A receptor (GABA). a NMT activates the downstream AC5-cAMP-PKA signaling pathway, thereby improving abnormal emotional states such as anger and depression. Through network pharmacology, molecular docking, micro-thermophoresis experiments, animal behavioral experiments, and cell experiments, NMT significantly improves the behavior of model animals. Therefore, this invention reveals for the first time that NMT improves abnormal emotional states such as anger and depression through GABA. a The mechanism by which R-related signaling pathways play a role in mood regulation can be used to prepare drugs for treating mood disorders such as anxiety, depression, and post-traumatic stress disorder, and has good application prospects.

The present application relates to a kind of bone-targeted trimeric protein and its preparation method and application, belong to biomedical technology field.The present application provides a kind of recombinant trimeric protein based on trimeric motif, including nuclear factor κB receptor activation factor extracellular segment, it is verified with in-vivo and in-vitro experiment with high bone targeting, possess inhibiting osteoclastogenesis and promoting osteoblast differentiation Dual control activity, it can also induce CD4 + Treg cell development, improve the bone marrow inflammatory microenvironment of osteoporosis model mice, can be used as the drug of osteoporosis, solves the problem that traditional single-function treatment drug in prior art will cause bone resorption rebound and bone loss after stopping drug, and further induces inflammation, provides new ideas and means for the research and treatment of osteoporosis, has good application prospect.

Procedures for inhibiting hormone receptor activation include administering to a subject in need of hormone receptor inhibition a compound having a chemical structure of a molecule that, when docked in the PPIase pocket, could disrupt proline-rich loop conformation and interactions. Procedures for treating prostate cancer or breast cancer include administering to a subject having prostate cancer or breast cancer a compound having a chemical structure of a molecule that, when docked in the PPIase pocket, could disrupt proline-rich loop conformation and interactions.

Disclosed herein are prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role by administering a compound disclosed herein to a subject in need thereof.

The present invention relates to a benzimidazolone-based cinnamamide derivative as a TRPV1 antagonist and a pharmaceutical composition for treating or preventing pain containing the same as an active ingredient. The example compounds provided in one aspect of the present invention block the activation of TRPV1 caused by capsaicin, a TRPV1 receptor activator, but induce appropriate inhibition at approximately pH 20% to 80%, thereby the compounds have pain-relieving effects and effectively reduce side effects such as abnormal body temperature.