51 results about "Kinase Family" patented technology

The invention provides methods of treating a disease selected from systemic sclerosis, rheumatoid arthritis, mastocytosis, and chronic eosinophilic leukemia comprising administering biaryl meta-pyrimidine compounds having the general structure (A) to a subject in need thereof. The pyrimidine compounds of the invention are capable of inhibiting kinases, such as members of the JAK kinase family, and various other specific receptor and non-receptor kinases.

The present invention describes polynucleotides that have been discovered to correlate to the relative intrinsic sensitivity or resistance of cells, e.g., lung cell lines, to treatment with compounds that interact with and modulate, e.g., inhibit, protein tyrosine kinases, such as, for example, members of the Src family of tyrosine kinases, e.g., Src, Fgr, Fyn, Yes, Blk, Hck, Lck and Lyn, as well as other protein tyrosine kinases, including, Bcr-abl, Jak, PDGFR, c-kit and Ephr. These polynucleotides have been shown, through a weighted voting cross validation program, to have utility in predicting the resistance and sensitivity of lung cell lines to the compounds. The expression level of some polynucleotides is regulated by treatment with a particular protein tyrosine kinase inhibitor compound, thus indicating that these polynucleotides are involved in the protein tyrosine kinase signal transduction pathway, e.g., Src tyrosine kinase. Such polynucleotides, whose expression levels correlate highly with drug sensitivity or resistance and which are modulated by treatment with the compounds, comprise polynucleotide predictor or marker sets useful in methods of predicting drug response, and as prognostic or diagnostic indicators in disease management, particularly in those disease areas, e.g., lung cancer, in which signaling through the protein tyrosine kinase pathway, such as the Src tyrosine kinase pathway, is involved with the disease process.

The invention searches the novel micromolecule inhibitor pyrazolo (1, 5-a) miazines compounds of cyclin-dependent kinase CDK9 (cyclin-dependent kinase) through the virtual screening of a computer, biometrically measures activity thereof, and validates interaction mechanism. The invention specifically comprises the following steps: the three-dimensional crystal conformation of the cyclin-dependent kinase family member CDK9 is obtained in a way of homology modeling; and micromolecule three-dimensional database is screened with DOCK (molecular docking). The invention uses a MTT tumor cell growth inhibition test to biometrically measures the activity of the selected compounds, researches the selected compounds pyrazolo (1, 5-a) miazines with high activety in a way of molecular mechanism, validates the inhibiting effect of the compounds to the activity of CDK9 kinase, and clarifies the interaction mechanism of the compounds for inhibiting the external activity and the molecule of various malignancies such as lung cancer, osteosarcoma, oophoroma, cervical carcinoma, breast cancer, etc.

There are provided compounds of formula I,wherein R, R1, Ra, Rb, Q, X and Y have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

The invention provides methods of treating a disease selected from systemic sclerosis, rheumatoid arthritis, mastocytosis, and chronic eosinophilic leukemia comprising administering biaryl meta-pyrimidine compounds having the general structure (A) to a subject in need thereof. The pyrimidine compounds of the invention are capable of inhibiting kinases, such as members of the JAK kinase family, and various other specific receptor and non-receptor kinases.

Compounds having the general structure (A) are provided. The compounds of the invention are capable of inhibiting kinases, such as members of the Src kinase family, Vegfr and various other specific receptor and non-receptor kinases.

Compounds of general Formula (I):wherein R1, R2, R3, Ra, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and / or the glycogen synthase kinase 3 family and are useful in preventing and / or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.

Various thienopyrimidine-based analog compounds are able to selectively inhibit the Src family of tyrosine kinases. Compounds of the present invention, capable of such selective inhibition, are of the basic structure seen in formulae (I), (II) or (III):These compounds are useful in the treatment of a wide variety of diseases including hyperproliferative diseases, hematologic allergic / immunological diseases, or viral infections. Methods of synthesis of these compounds and their methods of inhibiting the Src family of tyrosine kinases are presented.

2-((1r,4r)-4-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)cyclohexyl)acetonitrile compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions mediated by JAK, such as inflammatory bowel disease.

The invention discloses an associated protein for regulating and controlling round-leaf characteristics of cucumbers as well as a coding gene thereof and application thereof. An amino acid sequence ofthe protein is as shown in SEQ ID NO:2; protein kinase, which belongs to an AGC kinase family, of serine / threonine is coded by a PID gene; a coding gene of the protein is a base sequence as shown ina sequence table SEQ ID NO:1; guanine (G), at a site 1092bp, of the base sequence is substituted by adenine (A), Val (valine) at a site 346 of a coded amino acid residue sequence is mutated to be Met(methionine); the protein inhibits polar translocation of auxin, causes polar defect of auxin transport, has a blade edge smooth plant phenotype, has unapparent saw-tooth bugles, and has nearly roundleaves; a main root is not developed, and a main lateral root does not have obvious difference; male and female flowers are free of calyxes, and female flowers are not developed and the like. The geneand the protein can provide a basis for improving cucumber leaf type, increasing the yield, cultivating ideal plants and researching an auxin signal channel molecule regulation mechanism.

The present invention relates to a novel family of kinases inhibitors. Compounds of this class have been found to have inhibitory activity against members of the TEC kinase family, particularly BTK. The present invention is directed to a compound of Formula I or pharmaceutically acceptable salt, solvate, solvate of salt, stereoisomer, tautomer, isotope, prodrug, complex or biologically active metabolite thereof, for use in therapy.

The invention discloses a 5-substituted difluoro piperidine compound capable of penetrating blood brain barrier, wherein the compound has a structural formula represented by a formula (I). According to the present invention, the 5-substituted difluoro piperidine compound, the derivative and the pharmaceutical salt thereof can unexpectedly penetrate blood brain barrier, can have the pharmaceuticalproperties of protein kinase inhibitors, can particularly treat vascular endothelial growth factor receptor 2 or SRC kinase family (FYN)-mediated medical conditions, can further be used for treating or preventing abnormal protein kinase activity related disorders such as cancer, cancer brain metastasis, primary brain cancers such as glioma, malignant glioma, cancer meningeal metastasis, Alzheimer's disease, neurological diseases and the like.

2-((1r,4r)-4-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)cyclohexyl)acetonitrile compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions mediated by JAK.

The present invention relates to a newly identified family of protein serine / threonine kinases which phosphorylate microtubule-associated protein 2 (MAP2). It is based, in part, on the cloning and characterization of novel MAP2 kinases designated extracellular signal-regulated kinase 1, 2, and 3 (ERK1, ERK2, ERK3) which are expressed in the central nervous system, and on the identification of another ERK family member, ERK4, with antisera. The present invention provides for recombinant nucleic acid molecules and proteins representing members of the MAP2 kinase family, and also for microorganisms, transgenic animals, and cell lines comprising recombinant MAP2 kinase molecules. In additional embodiments of the invention, the present invention provides for methods for assaying cellular factor activity, including, but not limited to, nerve growth factor activity, in which the activation of MAP2 kinase serves as an indicator of cellular factor activity. These methods may be extremely useful in screening compounds for the presence of a desired cellular factor activity. In specific embodiments, compounds which may be useful in the treatment of Alzheimer's disease, peripheral neuropathies, and diabetes may be identified using the methods of the invention.

2-((1r,4r)-4-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)cyclohexyl)acetonitrile compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions mediated by JAK, such as inflammatory bowel disease.

The present invention is directed to treating a subject suffering from a disorder mediated by cell proliferation, such as cancer, by administering a fragment of focal adhesion kinase family kinase-interacting proteins. This method can involve regulating tumor formation or tumor growth in the subject. In addition, the present invention relates to the use of these proteins for regulating G1 to S phase progression of a cell, regulating the expression of p21 in a cell, regulating the phosphorylation of retinoblastoma protein in a cell, regulating retinoblastoma protein / E2F transcription factor 1 complex formation in a cell, regulating detachment-induced apoptosis of a cell, and regulating anchorage-independent growth of a cell.

2-((1r,4r)-4-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)cyclohexyl)acetonitrile compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions mediated by JAK.

The present invention relates to a newly identified family of protein serine / threonine kinases which phosphorylate microtubule-associated protein 2 (MAP2). It is based, in part, on the cloning and characterization of novel MAP2 kinases designated extracellular signal-regulated kinase 1, 2, and 3 (ERK1, ERK2, ERK3) which are expressed in the central nervous system, and on the identification of another ERK family member, ERK4, with antisera. The present invention provides for recombinant nucleic acid molecules and proteins representing members of the MAP2 kinase family, and also for microorganisms, transgenic animals, and cell lines comprising recombinant MAP2 kinase molecules. In additional embodiments of the invention, the present invention provides for methods for assaying cellular factor activity, including, but not limited to, nerve growth factor activity, in which the activation of MAP2 kinase serves as an indicator of cellular factor activity. These methods may be extremely useful in screening compounds for the presence of a desired cellular factor activity. In specific embodiments, compounds which may be useful in the treatment of Alzheimer's disease, peripheral neuropathies, and diabetes may be identified using the methods of the invention.

Uses of MAPK4, a member of the mitogen-activated protein (MAP) kinase family, are provided herein, based on the discovery that the MAPK4 negatively regulates the expression of genes associated with disease (e.g. PR-genes) and wound responses in plants such that the loss of MAPK4 function leads to their derepression. Methods are disclosed for controlling the growth of a plant and / or the expression of at least one wounding or pathogen response gene in said plant, the method comprising altering in the plant the level of the gene product of a MAPK4 gene. Furthermore, transgenic plants transformed with an MAPK4 construct and having enhanced wound and / or disease resistance are disclosed.

A novel polypeptide and a novel polynucleotide encoding the same are disclosed. The polypeptide is SMG-1, a protein included in the phosphatidyl inositol kinase related kinase family, and is useful in constructing a screening system for agents of treating and / or preventing a disease caused by a premature translation termination codon generated by a nonsense mutation.

There are provided compounds of formula I,wherein R1 to R5, X1, X2, Ar, L, A, A1, E and G have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

The invention discloses a compound with a general formula I, or a pharmaceutically acceptable salt, a stereoisomer, an ester, a prodrug, a solvate and a deuterated compound thereof, a composition containing the compound with the general formula I, and application of the compound with the general formula I or the pharmaceutically acceptable salt, stereoisomer, ester, prodrug, solvate and deuteratedcompound thereof in preparation of medicines for treating diseases related to serine / threonine kinase family (MAP4Ks), preferably medicines for treating diseases related to hematopoietic stem cell kinase 1 (HPK1).

The present invention relates to therapeutic protocols and pharmaceutical compositions designed to target HBx mediated activation of Src kinase, members of the Src tyrosine kinase family and components of the Src kinase family signal transduction pathways for the treatment of HBV infection and related disorders and diseases, such as HCC. The invention further relates to pharmaceutical compositions for the treatment of HBV infection targeted to HBx and its essential activities required to sustain HBV replication. The invention is based, in part, on the Applicants' discovery that activation of Src kinase signaling cascades play a fundamental role in mammalian hepadnavirus replication. Applicants have demonstrated that HBx mediates activation of the Src family of kinases and that this activation is a critical function provided by HBx for mammalian hepadnavirus replication.

The invention discloses a small molecule inhibitor compound as well as a preparation method and application thereof. The compound has a structure in a formula I show in the specification. The small molecule inhibitor compound provided by the invention overcomes the defects that the conventional drug only aims at a single drug target, and for a cancer at a later period and with a complex mechanism, the activity is low, drug tolerance is easy to generate and the activity is relatively low existing in the conventional drug. The small molecule inhibitor compound provided by the invention restrains VEGFR and EGFR receptor kinase families at the same time, has efficient antitumor activity and efficient antiinflammatory activity, and can be used for preparing efficient drugs for resisting tumors, inflammation, neuroinflammation and obesity.

The present invention is directed to compounds and pharmaceutically acceptable salts thereof which are inhibitors of the activity or function of the phosphoinositide 3'OH kinase family (hereinafter PI3K) for use in the treatment or prevention of respiratory infections, the treatment of airway damage, and / or the prevention of airway injury in patients with a PI3K Delta mutation.

Disclosed herein are JAK inhibitors that have low systemic toxicity. In some aspects, the disclosure includes methods for treating disease states, disorders, and conditions mediated by JAK, such as stomacho-intestinal system cancers, including colorectal cancers and familial adenomatous polyposis.