37 results about "Receptor activation" patented technology

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.

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 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 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.

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.

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.

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.

The subject matter described herein is directed to somatostatin receptor activating compounds, methods of making the compounds, pharmaceutical compositions, and their use in the treatment of diseases associated with somatostatin receptors.

The invention relates to the technical field of bioinformatics, and discloses an immunocompetence prediction method and system for NK cell culture, and the method comprises the following steps: collecting surface receptor signal intensity, cell factor secretion rate, culture solution metabolism characteristic parameters and cell population morphological indexes in the NK cell culture process; performing normalization and time sequence reconstruction on the parameters to form a receptor activation trend, a secretion rate change track, a metabolic flux fluctuation curve and a morphological uniformity vector; constructing a logic judgment path based on the factor groups, and sequentially identifying the immune activation state, the metabolic failure risk and the system stability; and mapping the judgment result into an immunocompetence prediction state diagram, and outputting high-activity, medium-activity or low-activity prediction results in combination with the evolution trend of the node trajectory. According to the NK cell immunocompetence prediction method, through multi-parameter collection and sequential processing, unified evaluation of the immune function, metabolic adaptation and morphological stability is achieved, and the comprehensiveness and reliability of NK cell immunocompetence prediction are improved.

The invention relates to a kit and a system for diagnosing diabetes. The kit includes several cells to contain several concentrations of an HDAR2 receptor activator or an HDAR3 receptor activator or an ester aqueous solution thereof. The kit provided by the invention can be used for effectively diagnosing diabetes mellitus by evaluating the sensitivity degree of a 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 wards, physical examination centers, homes and the like, and is an objective, quick and effective biological detection means for diabetes risk early warning.

A medicinal agent for the prevention and / or treatment of diseases caused by EP4 receptor activation is disclosed. A compound having antagonistic activity against the EP4 receptor is contained as an active ingredient in the medicinal agent. The compound represented by the following general formula (I) as defined in the specification, a salt, an N-oxide, or a solvate thereof, or a prodrug of these is useful as a medicinal component having antagonistic activity against the EP4 receptor for the prevention and / or treatment of diseases caused by EP4 receptor activation.

The invention provides a high-sensitivity in-vitro pyrogen detection method, which is characterized in that on the basis of an in-vitro pyrogen detection method (reporter gene method), a transgenic cell which expresses a Toll-like receptor and transfects an NF-kB reaction element and a luciferase gene is used for detecting a pyrogen, the pyrogen is combined with the Toll-like receptor on the surface of the cell to activate an NF-kB signal channel, and the NF-kB reaction element and the luciferase gene are converted into the NF-kB signal channel. Therefore, the expression of luciferase is activated.

This invention relates to the technology of antibodies, and more specifically, to antibodies that bind to the IL-18 receptor, IL-18 receptor activators, and their use. The invention provides antibodies that specifically bind to IL-18R1 and IL-18RAP with high affinity, and further provides bispecific antibodies that can efficiently bind both IL-18R1 and IL-18RAP simultaneously. These bispecific antibodies are novel IL-18 receptor activators that can activate the intracellular signaling pathway mediated by IL-18R1 / IL-18RAP, exert biological functions similar to IL-18 both in vitro and in vivo, and possess broad immunostimulatory effects and remarkable antitumor activity. Furthermore, they possess controllable activating activity, excellent molecular stability, and in vivo pharmacokinetic characteristics, which are advantageous for fully exhibiting antitumor efficacy in vivo, and offer prospects for a wide range of antitumor clinical applications.

It provides a modulator of receptor activation associated with specific diseases and / or conditions. [Solution] A modulator of RAGE activity is provided, wherein the RAGE activity is induced by an active coexisting GPCR.

Incorporation of lipids into scalp skin 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, and mixtures thereof; 2) 0.05 to 8.0% of a "gene activator material" that modulates the biosynthesis of lipids in the scalp skin, 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 mixtures thereof; and a cosmetically acceptable carrier.

Embodiments of the present disclosure disclose a use of a composition in the preparation of a retinoic acid X receptor gamma activator, the composition comprising phytol, teprenone, and silybin. Embodiments of the present disclosure also disclose a use of the composition in the preparation of an extracellular matrix metalloproteinase inhibitor and an interleukin-6 inhibitor at a specific ratio.

The invention discloses a self-adjuvant gel and an application of the self-adjuvant gel in tumor immunotherapy. According to the gel, N-acetylcysteine (NAC) is grafted with chitosan to form a sulfydryl-containing functional carrier, and the activity of T cells is effectively maintained by utilizing the interaction between NAC and sulfydryl on the surfaces of the T cells; meanwhile, the oxidized beta-glucan has Toll-like receptor 4 activation capability, and can promote the maturation and activation of dendritic cells. The formation of the gel depends on a Schiff base reaction between an aldehyde group in the oxidized beta-glucan and an amino group of the chitosan, and self-assembly gel formation under a mild condition is realized. The system can load a chemotactic factor CXCL9 and a tumor antigen at the same time, efficient recruitment of T cells is achieved by continuously releasing the CXCL9, and the antigen is synchronously and slowly released to induce specific immune response. The self-adjuvant gel has the functions of immune cell recruitment, antigen delivery and immune activation, and provides a novel material platform and strategy for tumor immunotherapy.

The application provides a system for on-demand regulation of cell behavior based on host-guest recognition space reversible rearrangement of cell receptors and application thereof, and the system comprises a beta-cyclodextrin polymer, a Met binding nucleic acid aptamer labeled with ferrocene and adamantane. Linear beta-cyclodextrin polymer and cross-linked beta-cyclodextrin polymer are used in the system. The two kinds of beta-cyclodextrin polymers have different regulation effects on cell receptors. The system composed of linear beta-cyclodextrin polymer can sensitively rearrange Met receptors to significantly inhibit HGF-induced Met receptor activation, block related signal pathways and indirectly regulate cell behavior. The system composed of cross-linked beta-cyclodextrin polymer can activate cell receptors and directly regulate cell behavior. The system can be applied to preparation of a detection kit for cell analysis and preparation of a drug for cell regulation to regulate the phosphorylation level of Met receptors, cell proliferation and cell migration behavior on demand.

The invention discloses a high-throughput and high-sensitivity screening method for endogenous itching-causing substances and application of the high-throughput and high-sensitivity screening method. According to the invention, firstly, endogenous itching-causing substances are screened out through a metabonomics technology, and then are verified through combination of a NanoBiT-based MRGPR detection system and an in-vivo experiment, so that integrated screening of the endogenous itching-causing substances in systemic disease itching is realized, and the defects of single discovery and screening mode of pruritus in systemic disease itching at present, low screening efficiency and the like are overcome. And breakthrough progress is not made yet. A cholestatic pruritus mouse is taken as an object, and the endogenous substance LPC (18: 1) screened from the cholestatic pruritus disease has strong activation and selectivity of the Mrgpra1 pruritus receptor, and can be used as an Mrgpra1 pruritus receptor agonist tool molecule for screening a tool medicine taking the Mrgpra1 pruritus receptor as a target spot.

Provided herein is a method for user controlled gene expression. In one embodiment, provided is a method for the activation of a T cell, comprising the steps of ectopically expressing farnesoid X receptor (FXR) in said T cell; activating said FXR; and transcribing a gene that contains a farnesoid response element (FRE) in a promoter region.