45 results about "Phosphorylation Inhibition" patented technology

The present inventions features methods for treating or preventing cancer (e.g., cancer of the central nervous system) by administering a compound that inhibits PAK kinase activity and/or merlin phosphorylation to a mammal (e.g., a human). The invention also provides screening methods for identifying additional inhibitors of PAK kinase activity and/or merlin phosphorylation.

The use of compositions which include one or more inhibitors of the citric acid, TCA, cycle and/or one or more inhibitors of oxidative phosphorylation for the treatment of cellular proliferation is disclosed. The composition is administered to or in the region of the proliferating cells or in a resection scar or cavity.

The present invention provides methods for use of IL-21 in combination with a tyrosine kinase inhibitor (TKI) in treatment of diseases in which inhibition of phosphorylation via TK inhibition and modulation of immune function play a clinically beneficial role. These diseases include, but are not limited to, cancers, such as renal cell carcinoma and metastatic melanoma.

Included in the present invention are methods of inhibiting sperm capacitation, inhibiting the phosphorylation of a protein at tyrosine residues, inhibiting an acrosomal reaction, and inhibiting fertilization of an egg by sperm with the administration of a CRISP polypeptide.

The invention discloses a nano-drug of a hybrid membrane loaded oxidative phosphorylation inhibitor and a preparation method of the nano-drug, and relates to the technical field of drug carriers. The nano-drug comprises an inner core and a shell; the outer shell covers the periphery of the inner core; the inner core comprises ROS-responsive drug-loaded nano-particles; drugs loaded by the ROS-responsive drug-loaded nano-particles are oxidative phosphorylation inhibitors; and the shell is a mixed membrane of a mitochondrial membrane and a tumor cell membrane. The nano-drug can cross BBB and reach a tumor site by virtue of homologous targeting of the tumor cell membrane, and can perform homologous target and can enter mitochondria by virtue of the mitochondrial membrane, the ROS-responsive drug-loading nano-particle is in a high-level ROS environment of the mitochondria, the core swells and degrades to release the loaded substance oxidation phosphorylation inhibitor, therefore, safe and efficient targeted drug therapy is realized. Through wrapping of the shell, the defect that the half-life period of the loaded medicine in the blood is short is avoided, and long circulation of the medicine in the blood is protected to a great extent.

The present invention relates to methods for determining the effectiveness of one or more agents for treating one or more disorders associated with aberrant cellular proliferation. Screening assays for the discovery of agents that alter eIF2α phosphorylation, inhibit translation initiation and/or inhibit aberrant cellular proliferation are also provided.

The invention discloses a research method for the pharmacologic action of mangiferin on mouse diabetes. The research method comprises material selection and an experimental method, biochemical parameter evaluation, histological analysis, measurement of reactive oxygen species (ROS), determination of malondialdehyde (MDA) and antioxidase, analysis of renal tissue inflammatory factors, immunofluorescent staining, Western blotting and statistic analysis. According to the research method, a trichrome staining method is utilized to observe renal morphology; a kit is utilized to determine a blood biochemical index; levels of inflammatory cytokines, the antioxidase, the MDA and the ROS are determined; expression of fibronectin, collagen I and alpha-SMA is detected by an immunohistochemical method, and regulation of paths of TGF-beta 1 and phosphatase and tensin homolog/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PTEN/PI3K/Akt) is detected by Western blotting; researches show thatthe mangiferin can significantly improve the renal dysfunction of diabetic mice; renal interstitial fibrosis can be prevented by reducing positive expression of fibronectin (FN), collagen type I (ColI) and alpha-smooth muscle actin (SMA) during therapy with the mangiferin; and meanwhile, mangiferin increases the antioxidase, reduces phosphorylation of the PI3K and Akt, inhibits the renal interstitial fibrosis, and provides more theoretical foundations for clinical application of traditional Chinese medicine in treating diabetes.

PAK4 and JIK, both of which bind to MKK7 and directly phosphorylate MKK7, were found in the present invention. The present invention provides an inhibitor of c-Jun phosphorylation caused by JNK3 and a method for inhibiting the same, and an agent for preventing and/or treating a disorder attributable to c-Jun phosphorylation caused by JNK3 and a method for preventing and/or treating the same, all of which comprise inhibiting one member selected from the following: the binding of PAK4 to MKK7, the phosphorylation of MKK7 by PAK4, the binding of JIK to MKK7, and the phosphorylation of MKK7 by JIK. Further, the present invention provides a method for identifying a compound that inhibits the binding of PAK4 to MKK7, the phosphorylation of MKK7 caused by PAK4, the binding of JIK to MKK7, or the phosphorylation of MKK7 caused by JIK, as well as the compound obtained thereby. Furthermore, the present invention provides a pharmaceutical composition containing an effective amount of at least one member selected from the group consisting of the aforementioned compound and the aforementioned inhibitor.

A method for controlling circadian rhythm disorders is described, characterized by inhibiting the phosphorylation of BMAL1 by c-Jun N-terminal kinase 3 (JNK3) due to the interaction between JNK3 and BMAL1; a method for preventing and/or treating diseases caused by circadian rhythm disorders; and a method for identifying a compound that inhibit phosphorylation of BMAL1 by JNK3. Also provided are: an agent for controlling circadian rhythm disorders, having the above characteristics; an agent for treating and/or preventing diseases caused by circadian rhythm disorders; a compound obtained by the identification method described above; an agent for inhibiting the phosphorylation of BMAL1 by JNK3, containing the compound; an agent for recovering the suppressed transcriptional activity of the complexes containing BMAL1 and CLOCK and for inhibiting the phosphorylation the same, containing an agent for inhibiting the expression and/or function of JNK3; and a pharmaceutical composition containing one of these.

The invention provides a pyrrolo [2, 3-d] pyrimidine derivative targeting EGFR mutation as well as a preparation method and application thereof, and belongs to the field of chemical medicines. The derivative is a compound shown as a formula I, or a salt thereof, or a stereoisomer thereof. The compound disclosed by the invention is low in toxicity to normal cells, has an obvious inhibition effect on a lung cancer cell line, particularly has good selectivity on EGFR mutant cells HCC827, and has an obvious inhibition effect; meanwhile, the compound provided by the invention can effectively inhibit phosphorylation of EGFR. In addition, the compound provided by the invention has good inhibitory activity and selectivity on mutant EGFR. The compound disclosed by the invention can be used for treating lung cancer, particularly non-small cell lung cancer, has a relatively strong inhibition effect on EGFR mutant lung cancer, and is relatively low in toxicity; the compound can also be used for preparing tyrosine kinase inhibitors, especially EGFR phosphorylation inhibitors, and has good application prospects.

The invention belongs to the field of medicines, particularly discloses application of an active component 3,3',4'-trimethoxy ellagic acid of sanguisorba officinalis to preparation of antitumor medicines, and discloses the 3,3',4'-trimethoxy ellagic acid. The 3,3',4'-trimethoxy ellagic acid inhibits angiogenesis through down-regulation of VEGF expression and inhibition of phosphorylation of PI3K/AKT/mTOR, induces tumor cell apoptosis through activation of a Bax/Bcl-2/Caspase-3 pathway, has a dual-effect antitumor effect of inhibiting tumor angiogenesis and cytotoxicity, and has a good therapeutic effect during application to preparation of anticancer medicinal preparations.

The invention belongs to the field of natural medicines and in particular discloses application of galangin in inhibition of transcription and expression of an FAK (focal adhesion kinase) gene, inhibition of functions of FAK through phosphorylation, inhibition of cell adhesion, infiltration and migration and inhibition of tumour metastasis. The invention also relates to a galangin medicine prepared by adopting the conventional medicine preparation method, galangin can be combined with the conventional tumour treatment medicine and treatment method when being used, and treatment application is carried out by adopting the conventional oral, intravenous and intraperitoneal administration routes, so that a foundation is laid for further application of the galangin.

The invention discloses a combined drug composition for breast cancer immunotherapy and an application of the combined drug composition. The combined drug composition comprises an SR1664 inhibitor ineffective quantity and an immunologic test point blocking antibody in effective quantity. The invention further provides a tumor immunotherapy drug combination method. The inventor finds that SR1664 can be used for resisting tumor malignant progression of PPAR gamma phosphorylation mediated with CDK5. The tumor relevant macrophage phenotype and function in tumor microenvironment can be adjusted and controlled, so that the T cellular infiltration is improved, and the immunosuppression tumor microenvironment can be further reversed. Through synergism of the SR1664 and the immunologic test pointblocking antibody, tumor restraining can be further reinforced.

The invention relates to a Ku70 protein T455 site phosphorylation inhibitor and application thereof, in particular to application of the Ku70 protein T455 site phosphorylation inhibitor in preparationof a reagent for inhibiting cancer invasion and metastasis, a method for inhibiting intracellular Ku70 protein T455 site phosphorylation and cancer cells with inhibited invasion and metastasis capacity; and a new treatment way and a new research model are provided for cancer invasion and metastasis, especially lung cancer invasion and metastasis.

The invention discloses an A-FABP protein inhibitor and application thereof in the technical field of metabolic diseases and cardiovascular and cerebrovascular complications thereof. The active ingredient of the A-FABP protein inhibitor is cobitinib. The clinically marketed drug cobitinib is used for targeted inhibition of an A-FABP protein, and the pro-inflammatory biological activity of the A-FABP protein is inhibited by inhibiting phosphorylation of a JNK/c-Jun signal channel. The new application is developed on the basis of existing drugs, a large amount of early-stage research and development investment can be saved, meanwhile, the research and development period of the drugs is greatly shortened, and the research result provides candidate treatment drugs for various metabolic diseases.

The invention belongs to the technical field of pesticides, and relates to an acaricidal composition containing a mitochondrial oxidative phosphorylation inhibitor. The acaricidal composition comprises an active component A and an active component B, the active component A is a mitochondrial oxidation phosphorylation inhibitor compound, and the active component B is a compound shown as a formula (I). The pesticide composition or a preparation thereof disclosed by the invention can efficiently kill mites, quickly prevent pest mites from feeding and reduce the cardinal number of insects; and the action mechanism is unique, the control effect on various pest mites is stable and reliable, and the mite killing spectrum can be expanded.

The invention discloses application of a targeting STAT1 inhibitor in treatment of immune thrombocytopenia and a method. An STAT1 nuclear inhibitor ivermectin and an STAT1 activation inhibitor fludarabine are adopted, and the number of platelets of an immune thrombocytopenia mouse model is increased by injecting the activation inhibitor or the nuclear inhibitor. In the abovementioned way, the fludarabine is a fluorinated nucleotide analogue of arabinoside, is free of radioactivity and is a small-molecule phosphorylation inhibitor; meanwhile, the ivermectin is a small-molecule inhibitor introduced by an input protein alpha/beta 1 mediated cell nucleus, the ivermectin and the small-molecule inhibitor are high in bioavailability, are widely applied to treatment of various blood system diseases, are good in safety, are applied to treatment of the immune thrombocytopenia and are safe, effective and high in compliance.