56 results about "Tyrosine Protein Kinases" patented technology

The invention discloses a making method of compound I and drug composition and application to treat tumour, which is 3-nitrile quinoline derivant (I) as dual-inhibitor protein kinase of tyrosine and nitric oxide synthase, wherein G1, G2, G3, G4, X, Z and n are defined as instruction.

Heterocyclic pyrimidine compounds that modulate mutant-selective epidermal growth factor receptor (EGFR) and ALK kinase activity are disclosed. More specifically, the invention provides pyrimidines which inhibit, regulate and/or modulate kinase receptor, particularly in selectively modulation of various EGFR mutant activity and ALK kinase activity have been disclosed. Pharmaceutical compositions comprising the pyrimidine derivative,and methods of treatment for diseases associated with protein kinase enzymatic activity, particularly EGFR or ALK kinase activity including non-small cell lung cancer comprising administration of the pyrimidine derivative are disclosed.

The invention relates to application of a series of indazole bi-aryl urea compounds and pharmaceutically acceptable salts thereof serving as protein kinase inhibitors to preparation of medicaments for treating diseases relevant to protein kinase activity, including tumors, inflammations, diseases relevant to autoimmunity reaction and diseases relevant to stem cells. As proved by experimental study, the indazole bi-aryl urea compounds and the pharmaceutically acceptable salts thereof play important roles in medical treatment and adjusting the activities of kinases such as KIT, PDGF (Platelet Derivation Growth Factor)-alpha, PDGF-beta, CSF1R (Colony Stimulating Factor 1 Receptor), DDR1and FLT3 of an original and/or mutative receptor tyrosine kinase (RTK) family and/or CDK8 (Cyclin-Dependent Kinase 8), CDK11 and HIPK4 (Homeodomain Interacting Protein Kinase 4) and the like of a CDK family. Preferred protein kinases are Kit, PDGF-alpha, PDGF-beta and FLT3 of the RTK family as well as CDK8 and CDK11 of the CDK family.

The present invention relates to new organic compound, and is especially the preparation process of N-(2-methyl-5-nitro) phenyl-4-(3-pyridyl) pyrimidiyl-2-amine as the key intermediate for imatinib, which is tyrosine protein kinase inhibitor for treating chronic myeloid leukemia and other diseases, and its analog N- phenyl-pyrimidiyl-2-amine derivative. The target product may be prepared through condensation of 4-aromatic heterocycle-2-halogenated pyrimidine and substituted aniline in the presence of catalyst. The preparation process has low material cost, scientific synthesis path, high product yield and other advantages.

In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of Sodium-dependent Phosphate Transporter lsoform NaPi-3b protein (SLC34A2) with Proto- oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

The invention discloses application of 4', 5, 7-genistein in preparing rotavirus resisting medicine. The genistein can restrain damage of tyrosine protein kinase to cell junction by restraining activation, caused by rotavirus infection, of tyrosine protein kinase of intestinal epithelial cells, so that the intestinal epithelial cells are prevented from being damaged by rotavirus, the completeness of intestinal mucosa is protected, the symptom of rotavirus diarrhea is obviously reduced, and the lethality is reduced. Thus, when the genistein is used as a main active ingredient, high-efficient and low-toxicity specificity rotavirus diarrhea resisting medicine can be researched and developed hopefully.

A method of treating disorders associated with aberrant kinase activity, wherein the kinase is. Adaptor-associated protein kinase 1 (AAK1), Aurora Kinase A (AURKA), Aurora Kinase B (AURKB), Bruton's Tyrosine Kinase (BTK), Interleukin-1 receptor-associated kinase 3 (IRAK3), Protein tyrosine kinase 2 beta (PTK2B), Tyrosine-protein kinase Tec (TEC), Serine/threonine-protein kinase Wee1 (WEE1), Cyclin G-associated kinase (GAK), Large Tumour suppressor 1 Kinase (LATS1), Focal Adhesion Kinase (PTK2), Ribosomal protein S6 kinase alpha-1 (RPS6KA1) said method comprising degrading said kinase.

Quinazoline derivatives represented by general formula (1) and quinazoline complexes as protein kinase inhibitors, and their preparation methods are provided. Wherein, in general formula (1), at least one of R and R′ is a group containing an atom capable of coordinating with noble metals, m and n are either the same or different and are integers from 0 to 5. Said quinazoline complex as protein kinase inhibitor is formed by coordination compound containing noble metal and said quinazoline derivative ligand capable of coordinating with noble metal in the coordination compound. Used as tyrosine protein kinase inhibitors, Quinazoline derivatives and quinazoline complexes as protein kinase inhibitors provided by the present invention have exhibited good inhibitory effect on proliferation of various tumor cells including human breast cancer cells line (drug-resistant) MCF-7/A, human breast cancer cell line (sensitive) MCF-7/S, prostate cancer cell PC-3, keratinocytes Colo-16, human non-small cell lung cancer cell line A549, etc.

The invention provides an application a complex (NRG1-ERBB4 complex) of NRG1 (neuregulin1) and a tyrosine kinase receptor ERBB4 thereof in preparing medicaments for treating myocardial ischemia. The invention provides a medicament for treating the myocardial ischemia by using the NRG1-ERBB4 complex as a target. Preferably, the medicament is mesenchymal stem cells (MSC) modified by ERBB4 genes. ERBB4 is over-expressed in the MSC by lentivirus, and therefore, the expression of a ligand NRG1 of the ERBB4 is up-regulated in a feedback manner so as to form a medicament having an NRG1-ERBB4-NRG1 self-feedback channel, so that not only is the endurance capacity of the MSCC on an oxygen-deficient environment improved, but also the concentration of high-level NRG1 is kept by means of the NRG1-ERBB4-NRG1 self-feedback channel, a protection role of the MSC on myocardial cells is improved and enhanced, and a curative effect of the medicament for treating the myocardial ischemia is improved.

The invention discloses 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds, dimer compounds of the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds, a preparation method and use of the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds and the dimer compounds of the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds, and pharmaceutical compositions containing the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds. More specifically, the invention discloses the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds expressed by structural formulae I and II or III, the dimer compounds of the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds and the preparation method of the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds and the dimer compounds of the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds, and provides the use of the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds and the pharmaceutical compositions containing the 5,8-disubstituted-1,6-naphthyridine-7-carbonyl amide compounds in the treatment of diseases related to protein tyrosine kinase, in particular to c-Src, such as tumor diseases, by serving as a multi-target spot protein tyrosine kinase inhibitor.

The invention relates to a porcine anti-porcine reproductive and respiratory syndrome (PRRS) related SNP label in a tyrosine protein kinase JAK2 gene and application thereof. The porcine anti-porcine reproductive and respiratory syndrome related SNP label is located on the porcine tyrosine protein kinase JAK2 gene. The nucleotide sequence of the SNP label is shown as SEQ ID NO.1, wherein a to-be-tested pig with 81bp, 115bp, 151bp and 264bp basic groups respectively as T, A, G and A at the sequence belongs to a PRRS susceptible pig variety, and a to-be-tested pig with the four basic groups respectively as C, G, A and T belongs to an anti-PRRS pig variety. The molecular genetic label provided by the invention is not restricted by porcine age, gender and the like, can be used for early breeding of the anti-PRRS pig variety, and even can realize accurate screening of newborn pigs, thus greatly accelerating the breeding process of anti-PRRS pigs. The screening method is accurate, and has the advantages of simple operation, low cost, and high efficiency.

A method for the recombinant production and purification of a protein kinase selected from the group consisting of tyrosine protein kinases and serine/threonine kinases by expressing a nucleic acid encoding said kinase in a microbial host cell, forming inclusion bodies containing said kinase, isolating, solubilizing, naturing, and purifying said kinase wherein said purification is performed by hydrophobic interaction with an hydrophobic adsorbent under conditions whereby at least 70% of said protein kinase are not bound to said adsorbent and the protein kinase not bound to said adsorbent is recovered.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more of C-C motif chemokine 16, C-C motif chemokine 14, and Tyrosine-protein kinase receptor UFO as diagnostic and prognostic biomarker assays in renal injuries.

The present invention concerns compounds and their use to inhibit the activity of a receptor tyrosine kinase. The invention is preferably used to treat cell proliferative disorders such as cancers characterized by over-activity or inappropriate activity c-kit kinase.

The invention relates to a compound as shown in a formula (I), and an isomer, a deuterated substance, an active metabolite, a solvate or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition containing the compound or the isomer, the deuterated substance, the active metabolite, the solvate or the pharmaceutically acceptable salt thereof, and a Bruton's tyrosine protein kinase (BTK) inhibitor. The invention also provides application of the substances in treatment of tumors, autoimmune diseases, allergic diseases, inflammation and other diseases caused by BTK abnormality.

The invention provides a novel and effective tyrosine protein kinase inhibitor, its isomer, pharmaceutically acceptable salts and chemical protection form, and pharmaceutical composition of the novel tyrosine protein kinase inhibitor and a pharmaceutical carrier or a diluent. The novel tyrosine protein kinase inhibitor can effectively treat protein kinase abnormity-caused diseases, and can effectively inhibit c-Met or c-Met mutant, and ALK or ALK fusion protein.

The invention discloses a kit for detecting the mRNA (messenger ribonucleic acid) expression quantity of U BCR fusion gene, belonging to the field of biotechnology. The kit comprises a detection primer, a fluorescent probe, a cDNA (complementary deoxyribonucleic acid) first strand synthesis reagent, fluorescent quantitative PCR (polymerase chain reaction) mixed solution, a negative control and a positive control, wherein the detection primer and the fluorescent probe comprise a U BCR fusion gene primer, an internal reference gene ABL primer and a Taqman fluorescent probe. The U BCR fusion gene is mainly found in chronic neutrophilic leukaemia with Ph+, and the gene code is high in the activity of tyrosine protein kinase, so that cells perform excessive multiplication and differentiation in case of no independence on cell factors, and normal cell apoptosis is inhibited. The mRNA level of the U BCR fusion gene is detected by adopting fluorescent quantitative PCR, and the specificity and the sensitivity of the detection result are remarkably improved. Via the kit, a novel rapid, simple and convenient gene diagnosis technology is provided for diagnosis, prediction and prognosis, and chemotherapy for chronic neutrophilic leukaemia.

Cells are genetically modified to express a luminophore, e.g., a modified (F64L, S65T, Y66H) Green Fluorescent Protein (GFP, EGFP) coupled to a component of an intracellular signalling pathway such as a transcription factor, a cGMP- or cAMP-dependent protein kinase, a cyclin-, calmodulin- or phospholipid-dependent or mitogen-activated serine/threonin protein kinase, a tyrosine protein kinase, or a protein phosphatase (e.g. PKA, PKC, Erk, Smad, VASP, actin, p38, Jnk1, PKG, IkappaB, CDK2, Grk5, Zap70, p85, protein-tyrosine phosphatase 1C, Stat5, NFAT, NFkappaB, RhoA, PKB). An influence modulates the intracellular signalling pathway in such a way that the luminophore is being redistributed or translocated with the component in living cells in a manner experimentally determined to be correlated to the degree of the influence. Measurement of redistribution is performed by recording of light intensity, fluorescence lifetime, polarization, wavelength shift, resonance energy transfer, or other properties by an apparatus consisting of e.g. a fluorescence microscope and a CCD camera. Data stored as digital images are processed to numbers representing the degree of redistribution. The method can be used as a screening program for identifying a compound that modulates a component and is capable of treating a disease related to the function of the component.

The present invention relates to an antibody, which specifically binds to tyrosine-protein kinase receptor TIE-2 (TIE2) so as to possess functions of blood vessel normalization and stabilization through receptor phosphorylation, and relates to: an anti-TIE2 antibody; a nucleic acid encoding same; a vector comprising the nucleic acid; a cell transformed with the vector; a method for preparing the antibody; an agent for stabilizing blood vessels and a composition for treating angiogenesis-associated diseases, both of which comprise the antibody; and a composition for co-administration with a pharmaceutical composition for tumor or cancer treatment and with a composition other than an antibody binding to TIE2.