61 results about "Kinase signaling" patented technology

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.

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 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 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 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 compounds of formulae I and II

wherein 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.

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 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.

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.

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.

The invention provides an inhibitor for inhibiting P4H8 gene expression and application thereof in preparing drugs for treating hepatitis B virus (HBV). In HepG2.2.15 cells with stably expressed HBV, large-scale functional silencing of all kinase genes and autophagy genes in the human genome is performed. The P4HB gene screened through the experiment can inhibit the positive gene secreted by HBV and further determine the effective shRNA (short hairpin ribonucleic acid) segment of the positive gene P4HB. The inhibitor systematically illuminates the influence of the kinase and host cell autophagy on HBV replication, discloses the relationship of the kinase signal and autophagy regulation network among the HBV, host and liver cancer, and provides a new drug target spot and theoretical references for new-generation anti-HBV treatment.

The present disclosure relates to the engraftment and proliferation of cells in fat-associated lymphoid clusters (“FALCs” or “milky spots”), which may be used to generate functional ectopic tissue. The present disclosure further provides methods and compositions for grafting and proliferating cells, in FALCs by activating the lymphotoxin beta receptor (LTβR) and/or NF-κB-inducing kinase (NIK) signaling pathway. The present disclosure also provides for methods and compositions to establish ectopic liver tissue in FALCs (milky spots) and to use such ectopic liver tissue for therapeutic benefit, and provides methods and compositions to generate ectopic kidney tissue in FALCs, which can be used in a subject for therapeutic benefit.

The application provides use of a CSF-1R kinase inhibitor, i.e., a compound with a general formula (A) or pharmaceutically acceptable salts thereof in preparation of drugs for treating CSF-1R kinase signal transduction channel related diseases or drugs for regulating immunity. Shown by in-vivo and in-vitro researches, the compound can be used for remarkably inhibiting the activity of a CSF-1R kinase; the compound can be used for remarkably inhibiting proliferation of a CSF-1/CSF-1R-driven mouse myeloid leukemia cell line, inhibiting survival of CSF-1-induced macrophages and reversing M2-leant polarization phenotypes of the macrophages, and the effect is superior to that of a drug Pexidartinib on the market; in a TAMs-enriched tumor model (MC38 model), the compound can be used for remarkably antagonizing a tumor immunity inhibiting microenvironment, and a remarkable antitumor drug effect is embodied; and the compound has an inhibiting action on tumors insensitive to immunity check point drugs, can be used for strengthening the treatment effect of the immunity check point drugs and has a very good clinical application prospect.