73 results about "Kinase signaling" patented technology

This invention is generally directed to the use of Indazole Compounds for treating or preventing diseases associated with protein kinases, including tyrosine kinases, such as proliferative diseases, inflammatory diseases, abnormal angiogenesis and diseases related thereto, atherosclerosis, macular degeneration, diabetes, obesity, pain and others. The methods comprise the administration to a patient in need thereof of an effective amount of an indazole compound that inhibits, modulates or regulates tyrosine kinase signal transduction. Novel indazole compounds or pharmaceutically acceptable salt thereof are presented herein.

The present invention relates to methods for treating cancer comprising utilizing a combination of signal transduction inhibitors. More specifically, the present invention relates to combinations of so called cell cycle inhibitors with mitogen stimulated kinase signal transduction inhibitors, more specifically combinations of CDK inhibitors with mitogen stimulated kinase signal transduction inhibitors, more preferably MEK inhibitors. Other embodiments of the invention relate to additional combinations of the aforesaid combinations with standard anti-cancer agents such as cytotoxic agents, palliatives and antiangiogenics. Most specifically this invention relates to combinations of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one including salt forms, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor, in combination with one or more MEK inhibitors, most preferably N-[(R)-2,3-dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide. The aforementioned combinations are useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.

The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and / or inhibit abnormal cell proliferation.

Disclosed are compounds of Formula I, including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

The present invention relates to compounds which inhibit, regulate and / or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, macular edema, retinal ischemia, inflammatory diseases, and the like in mammals.

The present invention provides a method for enhancing the immune function of a memory T cell which comprises the step of coinhibting signalling via an inhibitory receptor which regulates T cell exhaustion and via the p38 MAP kinase signalling pathway in the T cell, and a method for treating and / or preventing an immune condition in a subject, which comprises the step of enhancing the immune function of a memory T cell in the subject by such a method. There is also provided a pharmaceutical composition or kit comprising an agent capable of inhibiting signalling via an inhibitory receptor which regulates T cell exhaustion, such as PD-1, and an agent capable of inhibiting the p38 MAP kinase signalling pathway.

Disclosed are compounds of Formula I, including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

Disclosed are compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

The invention relates to Regorafenib and a manufacture method thereof and particularly relates to a compound shown in formula (I) or a pharmaceutical salt or a hydrate. The compound shown in formula (I) or the pharmaceutical salt or the hydrate can be used as a pharmaceutical bulk drug. The invention also relates to a method for preparing the compound shown in formula (I) or the pharmaceutical salt or the hydrate, and a pharmaceutical composition containing the compound shown in formula (I) or the pharmaceutical salt or the hydrate. The compound shown in formula (I) or the pharmaceutical salt or the hydrate can be used as a novel anti-tumour medicine for effectively treating the diseases mediated by abnormal VEGFR, PDGFR, raf, p38 and / or flt-3 kinase signal and the disease symptoms.

The invention discloses 3-heterocycle schiff base-5-fluorine-indole-2-ketone compounds represented by a general formula (I), pharmaceutical salts thereof, or solvent compounds thereof. R1, R2, R3, R4 and R5 are respectively independent unsubstituted C1-4 alkyl, unsubstituted C1-3 alkoxy, halogen, sulfamic, nitro, or hydrogen; or R1, R2, R3, R4 and R5 are respectively independent C1-4 alkyl substituted by 1 to 3 substituents selected from halogen, nitro, C1-3 alkyl, or C1-2 alkoxy; or R1, R2, R3, R4 and R5 are respectively independent C1-3 alkoxy substituted by 1 to 3 substituents selected from halogen, nitro, C1-3 alkyl, or C1-2 alkoxy. The halogen is fluorine, chlorine or bromine. X is S or NH. The invention also discloses a preparation method of the compounds, and an application of the compounds. The compounds provided by the invention assist in regulating the conduction of tyrosine kinase signals, and in inhibiting cacoethic cellular proliferation and blood vessel growth. The compounds provided by the invention provide substantial curative effects against diseases such as tumors, diabetes mellitus, dermatitis, and rheumatic arthritis.

The present invention provides compositions and methods for treating a tissue disorder associated with a response-to-injury process or proliferating cells in a mammal. These tissue disorders are associated with a novel cellular phenotype designated as “transition cells” which are described herein. This cellular phenotype is characterized in having an activated erk kinase signaling activity, a stimulated AP-1 binding activity, and at least one characteristic selected from the group consisting of: (a) increased podosome formation, (b) increased flux of intracellular or extracellular hyaluronans or hyaladherins, (c) increased expression of a hyaladherin, (d) an inability to form focal adhesions, (e) increased metalloproteinase activity, and (f) increased expression of a hyaladherin. Example tissue disorders include fibrosis, inflammation, degeneration and invasive disorders such as occur in cancerous cells. The methods provided herein include administering to the mammal, an effective amount of a composition that alters the activity of transition molecules within a cell Transition molecules are shown to be comprised of hyaladherins, hyaluronans and associated molecules that regulate the transitional phenotype. A novel cell culture comprising transition cells is also provided, as well as compositions comprising particular peptides, polypeptides, and antibodies that affect the transitional phenotype.

The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and / or inhibit abnormal cell proliferation.

The invention relates to a regorafenib tablet pharmaceutical composition and a preparation method thereof and in particular relates to a pharmaceutical composition. The pharmaceutical composition comprises an active pharmaceutical compound, a diluent, a disintegrating agent, an adhesive and a lubricating agent, wherein the active pharmaceutical compound refers to 4-[4-({4-chloro-3-(trifluoromethyl)phenyl]carbamyl}amino)-3-chlorophenoxy]-N-methylpyridine-2-formamide or pharmaceutically acceptable salts, solvates and polymorphism. The pharmaceutical composition has a contact angle of 40-100 degrees, particularly a contact angle of 40-90 degrees, preferably a contact angle of 40-80 degrees, and in particular a contact angle of 40-70 degrees. The pharmaceutical composition disclosed by the invention can be used for treating diseases and disease symptoms mediated by abnormal VEGFR, PDGFR, raf, p38 and / or flt-3 kinase signals. The invention also relates to a method for preparing an anti-tumor pharmaceutical composition. The pharmaceutical composition disclosed by the invention has excellent preparation performance.

The present invention relates to a method of treating ophthalmic diseases and conditions, e.g. diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, etc., in a subject comprising administering to said subject a therapeutically effective amount of at least one compound of formula Ior a prodrug, pharmaceutically acceptable salt, racemic mixtures or enantiomers of said compound. The compounds of formula I are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and / or inhibit abnormal cell proliferation.

The present invention relates to compounds of formulae I and IIwherein the variables are as defined herein. These compounds are capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and / or inhibit abnormal cell proliferation.

Disclosed are benzonaphthyridinyl derivative compounds and analogs thereof, pharmaceutical compositions comprising such compounds and processes for preparing the same. The compounds are useful in the treatment of diseases amenable to kinase signal transduction inhibition, regulation or modulation.

Disclosed is a complete plant MAP kinase cascade (e.g., MEKK1, MKK4 / MKK5, and MPK3 / MPK6) and WRKY22 / WRKY29 transcription factors that function downstream of the flagellin receptor FLS2, a leucine-rich-repeat (LRR) receptor kinase. Activation of such a MAPK cascade confers resistance to both bacterial and fungal pathogens. Also disclosed are disease-resistant plants expressing one or more members of this MAP kinase signaling cascade. Such members include constitutively active MEKK1 (ΔMEKK1), MKK4 (MKK4a), and MKK5 (MKK5a) or wild-type WRKY29.

The present invention provides compositions and methods for treating a tissue disorder associated with a response-to-injury process or proliferating cells in a mammal. These tissue disorders are associated with a novel cellular phenotype designated as “transition cells” which are described herein. This cellular phenotype is characterized in having an activated erk kinase signaling activity, a stimulated AP-1 binding activity, and at least one characteristic selected from the group consisting of: (a) increased podosome formation, (b) increased flux of intracellular or extracellular hyaluronans or hyaladherins, (c) increased expression of a hyaladherin, (d) an inability to form focal adhesions, (e) increased metalloproteinase activity, and (f) increased expression of a hyaladherin. Example tissue disorders include fibrosis, inflammation, degeneration and invasive disorders such as occur in cancerous cells. The methods provided herein include administering to the mammal, an effective amount of a composition that alters the activity of transition molecules within a cell Transition molecules are shown to be comprised of hyaladherins, hyaluronans and associated molecules that regulate the transitional phenotype. A novel cell culture comprising transition cells is also provided, as well as compositions comprising particular peptides, polypeptides, and antibodies that affect the transitional phenotype.

Disclosed are novel nitrogen-containing, heterocyclic, c-Met inhibitor compounds, processes for their preparation and formulations thereof. The compounds are useful as therapeutical agents for the inhibition, regulation, and control of c-Met kinase signal pathway, and useful for treating in a subject a cell proliferative disorder or disorders mediated by c-Met.

The present invention relates to drug delivery systems comprising ocular implant, which include organic molecules, capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and / or inhibit abnormal cell proliferation, in combination with a polymer, which polymer serves to control, modify, modulate and / or slow the release of the therapeutic component into the environment of the eye in which said composite is placed.

The invention generally relates to compositions and methods for identifying and testing tyrosine kinase signaling pathway agonists and antagonists, and more particularly, methods and compositions for screening compounds and identifying compounds that will modulate the interaction of protein tyrosine kinase substrates with their intracellular ligands, as well as between their intracellular ligands and other members of the signaling pathway.

The present invention relates to active polymorphs of 4-[2-(5-cyano-thiazol-2-ylamino)-pyridin-4-ylmethyl]-piperazine-1-carboxylic acid methylamide which inhibit, regulate and / or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angio-genesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, retinal ischemia, macular edema, inflammatory diseases, and the like in mammals.

A method based is provided for determining the toxicity of engineered nanomaterials (NM). The method comprises in vitro assays for oxidative stress associated with exposure to engineered NM, which comprise assays for: reactive oxygen species production; phase II and glutathione antioxidant molecule expression; activation of MAP and NF-kappa B kinase signaling cascades; production of cytokines, chemokines and adhesion molecules; mitochondrial perturbation and apoptosis; and cellular uptake and subcellular localization of the NM. The method further comprises in vivo assays for oxidative stress in subjects exposed to NM.

The subject invention concerns peptide molecules that specifically inhibit the enzymatic function of tyrosine kinases, including the JAK and EGF receptor (EGFR) family of kinases, to autophosphorylate, i.e., to transfer a phosphate group from ATP to an amino acid in the kinase. Phosphorylation of proteins is the most fundamental method for signal transduction among proteins in a cell. Inhibition of tyrosine kinase autophosphorylation activities inhibits the enzyme's signaling and shuts down the functioning pathways originating from the enzyme. The JAK2 and EGFR tyrosine kinases are involved in both inflammatory disorders and cancer. In these disorders, the tyrosine kinases can often be activated in an uncontrolled fashion. The subject application also concerns antibodies that bind to a tyrosine kinase autophosphorylation site. The subject invention also concerns pharmaceutically acceptable formulations of the subject peptides and antibodies, and methods for treating inflammatory and oncological disorders by inhibiting tyrosine kinase signaling in these situations by administering a peptide or antibody of the present invention.

The invention belongs to the field of biopharmacy and relates to 2-(quinazoline-4-amino)-5-thiazole carboxamide derivatives and a biological medicine use thereof. Based on a crystal structure of a compound of high-quality Src receptor tyrosine kinase and a Src receptor tyrosine kinase inhibitor saracatinib, a Src active pocket is defined, and a searching process is carried out on a known chemical storage by high-speed virtual screening software DOCK and an accurate scoring function so that the 2-(quinazoline-4-amino)-5-thiazole carboxamide small-molecular compounds having high inhibition activity to Src are obtained. A biological activity test proves that the 2-(quinazoline-4-amino)-5-thiazole carboxamide small-molecular compounds have strong inhibition activity to Src receptor tyrosine kinase, can be used for preparing antitumor drugs especially such as a drug for resisting Src kinase signal transduction system adjustment disorder-caused tumors, can be used as drug lead compounds for synthesis of a novel Src kinases inhibitor and especially can be used for treating Src-related tumor diseases.

Disclosed are compounds of Formula (I), including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR). Formula (I).

Described are compounds and methods useful in the promotion of muscle growth, the treatment of muscle loss or insufficient muscle growth, and the treatment of fibrotic conditions.

Compounds of the present invention concern 3-(1-{3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile hydrochloride solvates and crystalline modifications thereof. The compound, 3-(1-{3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile, has the following structural formula:The hydrochloride solvates and crystalline modifications thereof according to the invention are useful for treatment of physiological and / or pathophysiological conditions, such as cancer, that are caused, mediated and / or propagated by the inhibition, regulation and / or modulation of signal transduction of kinases, in particular by the inhibition of tyrosine kinases, especially Met-kinase. The present invention further relates to processes of manufacturing these crystalline modifications.

The present invention describes methods of inhibiting the pro-inflammatory response of human peripheral blood mononuclear cells or polymorphonuclear cells, or fixed tissue cells. The cells are contacted with a pro-inflammatory agent to stimulate a pro-inflammatory response. The cells are then contacted with G protein kinase signaling pathway modifiers, thereby inhibiting G protein mediated inflammatory response signaling pathways. The present invention describes receptor complexes wherein G protein kinase signaling pathway modifiers bind to cell surface receptors on human peripheral blood mononuclear cells or polymorphonuclear cells stimulated with proinflammatory agents.