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.

Xanthosine-5'-monophosphate is produced by cultivating the bacterium which has a resistance to growth inhibition by an inhibitor selected from the group consisting of inhibitors of cell membrane biosynthesis and / or functioning, phosphorylation inhibitors, uncoupling agents, RNA-polymerase inhibitors and methionine analogs, and has an ability to produce xanthosine-5'-monophosphate according to produce and accumulate xanthosine-5'-monophosphate in the culture, and recovering the xanthosine-5'-monophosphate therefrom.

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.

Methods of screening for candidate compounds capable of inhibiting activity of fyn in phosphorylating tau protein at Y394 or binding to fyn to inhibit interaction with tau protein at Y394, including determining whether, and optionally the extent, the candidate compounds have these capabilities under conditions where fyn has these capabilities in the absence of the candidate compound. Methods of screening for substances capable of promoting dephosphorylation of tau protein by a phosphatase at a site of tau protein including contacting a candidate substance, the tau protein and a phosphatase capable of dephosphorylating the tau protein under conditions where the phosphatase is capable of dephosphorylating the site in absence of the candidate substance, where the kinase is fyn; determining whether, and optionally the extent, the candidate substance promotes dephosphorylation of the tau protein at the site; and selecting the candidate substance which promotes dephosphorylation of the tau protein the sites.

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.

The present invention relates to an agent for use in selectively killing one or more senescent cells, wherein the agent is selected from the following: a cardiac glycoside or alglycone, a focal adhesion kinase (FAK) inhibitor, an HMG-CoA reductase inhibitor, JFD00244, Cyclosporine, Tyrphostin AG879, Cantharidin, Diphenyleneiodonium chloride, Rottlerin, 2,3-Dimethoxy-1,4-naphthoquinone, LY-367,265,Rotenone, Idarubicin, Dequalintum chloride, Vincristine, Nitazoxanide, Nitrofurazone, Temsirolimus, Eltrombopag, Adapalene, Azacyclonol, Enoxacin and Raltegravir, and pharmaceutically acceptable salts thereof. Another aspect relates to compounds for use in treating or preventing a senescence- associated disease or disorder, and methods relating thereto.

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 present invention relates to a method for in vitro phosphorylation of TRAP derived from Staphylococcus aureus. In the present invention, the TRAP is first identified as a kinase that self-phosphorylates and is phosphorylated specifically in the presence of an oxidative metal ion such as iron, copper and zinc. Based upon this finding, a novel method for in vitro phosphorylation of purified TRAP is provided and also, a method for screening various chemicals and natural materials by using the above method is provided in order to select inhibitors against the TRAP phosphorylation. The inhibitors are expected to be applied for novel antibiotics of Staphylococcus aureus, because this TRAP phosphorylation is essential to infect Staphylococcus aureus. Therefore, the present invention can be widely used to develop novel drugs against Staphylococcus aureus and their resistant strains, in near future.

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 present invention provides an isolated nucleic acid molecules encoding IκB kinase (IKK) catalytic subunit polypeptides, which are associated with an IKK serine protein kinase that phosphorylates a protein (IκB) that inhibits the activity of the NF-κB transcription factor, vectors comprising such nucleic acid molecules and host cells containing such vectors. In addition, the invention provides nucleotide sequences that can bind to a nucleic acid molecule of the invention, such nucleotide sequences being useful as probes or as antisense molecules. The invention also provides isolated IKK catalytic subunits, which can phosphorylate an IκB protein, and peptide portions of such IKK subunit. In addition, the invention provides anti-IKK antibodies, which specifically bind to an IKK complex or an IKK catalytic subunit, and IKK-binding fragments of such antibodies. The invention further provides methods of substantially purifying an IKK complex, methods of identifying an agent that can alter the association of an IKK complex or an IKK catalytic subunit with a second protein, and methods of identifying proteins that can interact with an IKK complex or an IKK catalytic subunit.

The invention provides an application of a reagent for losing CTTNBP2NL function in preparation of a medicine for treating diseases. Mainly provides an application of a reagent for losing CTTNBP2NL function in preparation of drugs for treating diseases caused by STAT3 protein phosphorylation. The reagent for deleting the CTTNBP2NL function is a reagent for inhibiting the expression of the CTTNBP2NL or a reagent for inhibiting the promotion of the phosphorylation activity of STAT3 protein in tumor cells by the CTTNBP2NL. Overexpression of CTTNBP2NL can cause the occurrence of diseases. The function of CTTNBP2NL is lost, so that phosphorylation of the STAT3 protein Y705 site in tumor cells can be effectively reduced, and tumor growth is inhibited; meanwhile, the function of CTTNBP2NL is lost, so that the generation of autoantibodies can be reduced, and systemic lupus erythematosus can be treated; the traditional Chinese medicine composition can also relieve the symptoms of rheumatic arthritis, inflammatory bowel disease, psoriasis and the like, and effectively treat rheumatic arthritis, inflammatory bowel disease, psoriasis and the like. Therefore, the CTTNBP2NL function-deficient reagent can be used for medicines for treating tumors, autoimmune diseases and neurological diseases, and has a good application prospect.

The present invention belongs to the field of tumor treatment and drug resistance detection, discloses a marker KIFC1 for predicting drug resistance and / or a recurrence rate and / or lifetime and / or treatment of tumors, and further discloses a molecular target for predicting the drug resistance and / or the recurrence rate and / or the lifetime and / or the treatment of tumors by phosphorylation of 26th serine of the KIFC1. The present invention also discloses a KIFC1 specific antibody and the antibody can be used as a detection index for predicting drug resistance and / or a recurrence rate and / or lifetime of tumors. The present invention also discloses a KIFC1 phosphorylation inhibitor. The inhibitor can be used for inhibiting an expression amount of a KIFC1 protein, inhibiting KIFC1 phosphorylation and functions thereof, inhibiting centrosome agglutination induced by the KIFC1 as a key factor, and can be used as an antitumor drug and a drug for reducing drug resistance and / or recurrence of tumors. The present invention aims to formulate corresponding strategies to reduce drug resistance and recurrence probability of tumors in a chemoradiotherapy process and reduce a survival rate of tumorcells. The marker KIFC1 and the inhibitor thereof have a wide application prospect in the field of treatment of tumors.

The invention belongs to the technical field of pesticides, and relates to an acaricidal composition containing a mitochondrial oxidative phosphorylation inhibitor. The active ingredients of the acaricidal composition include active ingredient A and active ingredient B; the active ingredient A is mitochondrial oxidized phosphoric acid Inhibitor compounds, the active ingredient B is a compound shown in formula (I). The pesticide composition or the preparation thereof of the present invention can efficiently kill mites, quickly prevent harmful mites from feeding, and reduce the population base of insects; the mechanism of action is unique, the control effect on various harmful mites is stable and reliable, and the spectrum of killing mites can be expanded.

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 provides an establishment method of a mouse motion model, and belongs to the field of biology. According to the establishment of the motion model, by setting parameters of running exercise, the situation that a mouse reaches a certain amount of exercise is ensured, and therefore a mouse subjected to exercise training is obtained. Data show that the weight of the mouse subjected to exercise training can be reduced, phosphorylation of liver AMPK protein of the mouse can be promoted, expression of liver fat synthesis and glycogen synthesis genes is inhibited, and the effect of being beneficial to liver health is shown. The motion model may become a means for researching mouse liver metabolism or an auxiliary method for treating liver metabolism related diseases.

Provides a dopamine trimer with a novel structure, that is, a dopamine trimer extracted from Jiuxiangworm, an insect traditional Chinese medicine that can warm the middle and help yang, and a pharmaceutical composition containing it, as well as its preparation for treating diabetic nephropathy or chronic kidney disease. application in medicine or health food. The clinical application of the theory of worm dredging collaterals shows that collaterals are related to microvascular lesions. Ninecyclopamide A can significantly inhibit high glucose-induced mesangial cell secretion of extracellular matrix and inflammatory factors, and is an inhibitor of Smad3 phosphorylation, which can significantly inhibit TGF-β1-induced Smad3 phosphorylation and Smad3 expression, in view of TGF-β / Smads signaling pathway is the main pathology mediating organ fibrosis, suggesting the application value of this compound in chronic kidney disease including diabetic nephropathy and renal fibrosis.

The invention relates to application of fexofenadine in preparation of a medicine for preventing and treating intervertebral disc degeneration. Research finds that fexofenadine can directly enter nucleus pulposus cells to be combined with cPLA2 in the cells after being injected into a body, cPLA2 phosphorylation is inhibited, then NF-kB phosphorylation is influenced, TNF-alpha mediated inflammatory reaction is inhibited, the cell stability is effectively protected, TNF-alpha induced cell apoptosis and inflammatory factor generation are further reduced, and the local inflammatory response is reduced by inhibiting the generation of the inflammatory factors. Besides, fexofenadine can also inhibit the generation of TNF-alpha mediated MMP-13 (cartilage matrix degrading enzyme), so that the destructive effect of the destructive enzyme on intervertebral disc tissues is reduced and prevented, and the integrity of the intervertebral disc tissues is kept. According to the application, the drug indications of fexofenadine are expanded, and a new drug treatment scheme is provided for preventing and treating intervertebral disc degeneration.

The present invention relates to a method for in vitro phosphorylation of TRAP derived from Staphylococcus aureus. In the present invention, the TRAP is first identified as a kinase that self-phosphorylates and is phosphorylated specifically in the presence of an oxidative metal ion such as iron, copper and zinc. Based upon this finding, a novel method for in vitro phosphorylation of purified TRAP is provided and also, a method for screening various chemicals and natural materials by using the above method is provided in order to select inhibitors against the TRAP phosphorylation. The inhibitors are expected to be applied for novel antibiotics of Staphylococcus aureus, because this TRAP phosphorylation is essential to infect Staphylococcus aureus. Therefore, the present invention can be widely used to develop novel drugs against Staphylococcus aureus and their resistant strains, in near future.

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.