28 results about "Orphan receptor" patented technology

The present invention relates to the use of an ROR inverse agonist or a pharmaceutically acceptable salt thereof for the preparation of a medicament for modulating ROR in a patient and / or for controlling autoimmune diseases and antibody-mediated rejection in a patient. The ROR-mediated diseases or autoimmune diseases include HIV, cancer, celiac disease, type 1 diabetes, Graves' disease (Graves' disease), inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, asthma, dermatitis, fatty liver disease, Crohn's disease (Crohn's disease), cardiovascular disease, inflammatory disease, nervous system disorders, multiple sclerosis, and the like. Acute respiratory distress syndrome and arteriosclerosis.

The present invention relates to bi-specific antigen binding molecules with specificity for both receptor tyrosine kinase-like orphan receptor 1 (ROR1) and epidermal growth factor receptor (EGFR) and associated fusion proteins and conjugates. In a further aspect, the present invention relates to conjugated immunoglobulin-like shark variable novel antigen receptors (VNARs).

ROR1-specific antigen-binders, and multispecific antibodies are provided, which contains one or more ROR1-specific antigen-binding sites and at least one antigen-specific binding site for an activation receptor (such as CD3) on an immune cell, wherein various configurations are presented of new VHH-based anti-ROR1 sequences in relation to the antigen-specific binding site for the immune cell activation receptor, as well as to a scaffolding segment forming a constant region of the antibodies. These multispecific antibodies have been demonstrated to bind to ROR1-positive cancer cells, induce immune cell-mediated cytotoxicity against ROR1-positive target cells, and to inhibit growth of tumor size in animals.

The present disclosure provides novel 4-substituted-phenyl acetamide and arylurea derivatives that act as agonists against GPR88. The compounds of the present disclosure are believed to be useful for the treatment of diseases and conditions caused by physiological processes implicating the orphan receptor GPR88, including diverse brain and behavioral functions such as cognition, mood, movement control, and reward-based learning. GPR88 is emerging as a novel drug target for central nervous system disorders including schizophrenia, Parkinson's disease, anxiety, and addiction. One particular indication for which GPR88 agonists hold promise is alcohol use disorder (AUD).

The present application relates to an isolated antigen binding protein capable of binding to ROR1 (Receptor Tyrosine Kinase Orphan Receptor 1), said isolated antigen protein comprising CDR1, CDR2 and CDR3. The present application also provides a method for preparing said isolated antigen binding protein and uses thereof.

The invention provides a method for determining an endogenous ligand of an orphan receptor and application of the method. Particularly, the endogenous ligand of GPR50 is identified, and the function of the endogenous ligand is characterized. The ligand-receptor pairing screening platform established by the invention has high sensitivity and wide generalizability.

Provided herein are, inter alia, antibodies (e.g., humanized antibodies, monoclonal antibodies), antibody fragments (e.g., scFvs), and antibody compositions (e.g., chimeric antigen receptors, bispecific antibodies) that bind to human tyrosine kinase-like orphan receptor 2 (ROR2) with high efficiency and specificity and are useful, inter alia, for the diagnosis and treatment of cancer and other ROR2-associated diseases.

Provided are a fusion polypeptide, an expression cassette comprising a coding gene thereof, a gene delivery vector, a pharmaceutical composition, and uses thereof. Specifically, the invention provides a fusion polypeptide, which comprises a secretion signal peptide and an afbercept polypeptide, and the secretion signal peptide is selected from any one of a human albumin secretion signal peptide, a human Opticin protein secretion signal peptide, a human interleukin-2 secretion signal peptide and a mouse receptor tyrosine kinase-like orphan receptor 1 secretion signal peptide. According to the fusion polypeptide, the polynucleotide for encoding the fusion polypeptide, the gene expression cassette containing the polynucleotide and the gene delivery vector containing the expression cassette, the expression of the aflibercept can be improved, and the effect of treating eye diseases by using the aflibercept can be improved.

The invention belongs to the technical field of fluorescent probes, and particularly discloses a novel fluorescent compound capable of being combined with a retinoic acid receptor related orphan receptor gamma normal site and application of the novel fluorescent compound serving as a fluorescent probe to inhibitor screening, imaging and the like. Compounds P1-P11 conforming to the general formula (I) are synthesized, a novel ROR gamma normal inhibitor screening platform can be established on the basis of a fluorescence polarization probe system constructed by the compounds according to a competitive ligand replacement principle, and the technical scheme breaks through the limitation of a traditional activity detection method and has a wide application prospect. An activity evaluation tool with economical efficiency, timeliness and reliability is provided for research and development of drugs targeting ROR gamma normal sites, and the lead compound discovery and structure optimization process can be accelerated.

The invention discloses a GPR21 expression vector and a construction method and application of a recombinant HEK293 cell based on the GPR21 expression vector, and belongs to the technical field of biology. PGMLV-CMV-HGPR21-EF1-ZsGreen1-T2A-Puro plasmids are constructed on the basis of a seamless cloning technology and are packaged into a lentivirus system for infecting HEK293 cells, puromycin is used for screening to obtain a genetic engineering cell line GPR21-HEK293 of stably transfected full-length GRP21, and the cell line is proved to be capable of improving the protein expression of the full-length GPR21 by 2.5 times, so that the gene engineering cell line GPR21-HEK293 can be used for efficiently expressing the full-length GPR21. The cell with high GPR21 expression provides a technical means for research on a ligand of a GRP21 orphan receptor and screening of drugs for treating inflammation, immunity, metabolism related diseases and the like by taking GRP21 as a target.

The application belongs to the technical field of pharmaceutical chemistry, and discloses a phenothiazine sulfonamide compound shown in a general formula (I) or a salt thereof, a preparation method and application thereof. The compound, a pharmaceutically acceptable salt, an isomer, a prodrug, a co-crystal complex, a hydrate or a solvate thereof can be used as an agonist of a retinoic acid receptor-related orphan receptor-gamma t (RORgamma t).

The invention encompasses the novel class of compounds represented by the Formula (I), (II), (III) and (IV) below, which are modulators of RORγtThe invention also encompasses pharmaceutical compositions which include the compounds shown above and methods of treating or preventing autoimmune diseases and antibody mediated rejection.

The present invention provides substituted tetrahydroquinolinone and related compounds of formula (I), which are therapeutically useful as modulators of Retinoic acid receptor-related orphan receptors (RORs), more particularly as RORγ modulators. These compounds are useful in the treatment and prevention of diseases and / or disorder, in particular their use in diseases and / or disorder mediated by RORγ receptor. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the substituted tetrahydroquinolinone or related compounds of formula (I), together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

The application belongs to the technical field of drug research and development, and particularly relates to a compound, a preparation method and application of the compound as an agonist of orphan receptor GPR99. The application first discovers and identifies a small-molecule compound capable of specifically activating the orphan receptor GPR99, and systematically clarifies the mechanism of the small-molecule compound in the regulation of vascular smooth muscle cell (VSMC) contraction and the improvement of pathological vascular dilation. The discovery not only fills the blank of GPR99 agonists in the field of treatment of rosacea, but also provides a new molecular target and a drug research and development direction for precise treatment of diseases related to abnormal vascular function.

The invention provides a transcription factor (ROR beta) of a biomarker retinoic acid-related orphan receptor beta (retinoic acid-related orphan receptor beta) and an application of the transcription factor in BD-related diseases, and the application comprises application of the biomarker in preparation of a bipolar affective disorder (bipolar affective disorder, BD-related diseases). The invention relates to a biomarker, a diagnostic product for BD-related diseases, a drug for treating and / or preventing BD-related diseases, and application of the biomarker in screening of drugs for treating and / or preventing BD-related diseases. The biomarker is a detection target of the diagnostic product and a treatment, prevention and / or screening target of the drug. According to the invention, the correlation between ROR beta and BD disease occurrence through a pancreas-hippocampus feedback loop mechanism is determined for the first time, and a plasma sample can be detected, so that the convenience of detecting and screening medicines is improved.

Provided is use of a substance capable of up-regulating ISG gene expression in preparing a drug or reagent for promoting the regeneration and repair capacity of tissues or complex structures or organs of mammals. The substance for up-regulating ISG gene expression is selected from one or two or more of an MAPK inhibitor, a retinoic acid receptor-related orphan receptor inhibitor, a protein synthesis inhibitor, and an interferon (IFNγ, β, λ) or alarmin (S100A8 / A9) protein. The regeneration and repair refer to promoting the regeneration of tissues or complex structures or organs after tissue or organ resection or damage.

The present invention relates to benzimidazole derivatives of formula (I) as inhibitors of the retinoid-binding orphan receptor gamma (RORγ) protein, pharmaceutical compositions containing the compounds, methods of preparing them, and the use of the compounds as therapeutic agents for the treatment of diseases or disorders mediated by RORγ.

Antibodies targeting receptor tyrosine kinase-like orphan receptor 1 and uses thereof are provided. Pharmaceutical compositions comprising the antibodies and uses are also provided. The provided antibody achieves excellent anti-tumor activity or / and better safety. The provided antibody can be used for tumor treatment.

The invention belongs to the technical field of medicine research and development, and particularly relates to a compound, a preparation method and application of the compound as an orphan receptor GPR99 agonist. The small molecule compound capable of specifically activating the orphan receptor GPR99 is found and identified for the first time, and the action mechanism of the small molecule compound in vascular smooth muscle cell (VSMC) contraction regulation and pathological vasodilation improvement is systematically clarified. The discovery not only fills the blank of the GPR99 agonist in the field of acne rosacea treatment, but also provides a new molecular target and a medicine research and development direction for precise treatment of vascular dysfunction related diseases.

The invention discloses application of receptor tyrosine kinase-like orphan receptor-1 as a target spot in preparation of a medicine for treating depression, and belongs to the technical field of biological medicine. The invention provides ROR1 as a new target for developing and treating depression. According to the invention, gene regulation and control viruses are respectively injected into island leaf cortex brain regions of mice, specific overexpression or knock-down of ROR1 in IC brain regions of the mice is carried out, and the depression behavior of the mice is evaluated by using behavioral technical means. Results show that specific overexpression of the IC brain region ROR1 causes depression behaviors of mice; on the contrary, the mouse depression phenotype caused by chronic unpredictable stress can be effectively improved by specifically knocking down the ROR1 in the IC brain region. The invention provides a new target for revealing new pathogenesis and treatment means of depression and developing a novel antidepressant drug, has potential clinical transformation application prospects, and can effectively improve the defects of short curative effect, large side effect and the like of the traditional antidepressant drug.

The present application relates to an isolated antigen binding protein capable of binding to ROR1 (Receptor Tyrosine Kinase Orphan Receptor 1), said isolated antigen protein comprising CDR1, CDR2 and CDR3. The present application also provides a method for preparing said isolated antigen binding protein and uses thereof.

The present invention discloses talaroterpene D, a sesquiterpene derived from a marine fungus, its preparation method, and its use in the preparation of RORα agonists. The structural formula of talaroterpene D is shown in Formula I. The present invention isolated talaroterpene D, a novel sesquiterpene derived from the fermentation culture of the marine fungus Talaromyces sp. SCSIO 41412, which stimulates the transcriptional activity of RORα and regulates downstream genes such as BMAL1. This compound, or a pharmaceutically acceptable salt thereof, can be used to prepare agonists for retinoic acid-related orphan receptor α.

The present invention relates to benzimidazole derivatives as modulators of retinoid-related orphan receptor gamma (RORy) and their pharmaceutical uses, in particular to benzimidazole derivatives of formula (I) as inhibitors of the retinoid-related orphan receptor gamma (RORy) protein, pharmaceutical compositions comprising the compounds, processes for their preparation, and the use of the compounds as therapeutic agents for the treatment of RORy-mediated diseases or conditions.

Provided herein, inter alia, are antibodies (e.g., humanized antibodies, monoclonal antibodies), antibody fragments (e.g., scFvs), and antibody compositions (e.g., chimeric antigen receptors, bispecific antibodies) that bind to human tyrosine kinase-like orphan receptor 2 (ROR2) with high efficiency and specificity and are useful, inter alia, in the diagnosis and treatment of cancer and other ROR2-related diseases.

The invention belongs to the technical field of medicine research and development, and particularly relates to application of a compound as an orphan receptor GPR85 agonist. According to the invention, the small molecule compound capable of specifically activating the orphan receptor GPR85 is discovered and identified for the first time, and the action mechanism of the small molecule compound in increasing synaptic density and improving social memory impairment is systematically clarified. The invention not only fills up the blank of the GPR85 agonist in the field of synaptic disease treatment, but also provides a new molecular target and a medicine research and development direction for precise treatment of social memory impairment related diseases.

The present invention relates to receptor tyrosine kinase-like orphan receptor I (RORI) specific antigen binding molecules and associated fusion proteins and conjugates. In a further aspect, the present invention relates to coajugated immunoglobulin-like shark variable novel antigen receptors (VNARs).

Provided herein are, inter alia, antibodies (e.g., humanized antibodies, monoclonal antibodies), antibody fragments (e.g., scFvs) and antibody compositions (e.g., chimeric antigen receptors, bispecific antibodies), which bind human tyrosine kinase-like orphan receptor 2 (ROR2) with high efficiency and specificity. The antibodies and antibody compositions provided herein include novel light and heavy chain domain CDRs and framework regions and are, inter alia, useful for diagnosing and treating cancer and other ROR2-related diseases.

The application belongs to the field of biological medicine and provides an antibody drug conjugate targeting receptor tyrosine kinase-like orphan receptor 1, wherein the antibody drug conjugate comprises an antibody, a linker and a cytotoxic drug connected in sequence. The application also provides a pharmaceutical composition comprising the antibody drug conjugate and uses thereof. The provided antibody drug conjugate achieves excellent antitumor activity or / and better safety. The provided antibody drug conjugate can be used for the treatment of tumors.