261 results about "Protein-Tyrosine Kinases" patented technology

The present invention relates to novel cytoplasmic tyrosine kinases isolated from megakaryocytes (megakaryocyte kinases or MKKs) which are involved in cellular signal transduction pathways and to the use of these novel proteins in the diagnosis and treatment of disease. The present invention further relates to specific megakaryocyte kinases, designated MKK1, MKK2 and MKK3, and their use as diagnostic and therapeutic agents.

Molecules comprising the antigen-binding portion of antibodies that block constitutive and / or ligand-dependent activation of a receptor protein tyrosine kinase, such as fibroblast growth factor receptor 3 (FGFR3), are found through screening methods, where a soluble dimeric form of a receptor protein tyrosine kinase is used as target for screening a library of antibody fragments displayed on the surface of bacteriophage. The molecules of the present invention which block constitutive activation can be administered to treat or inhibit skeletal dysplasia, craniosynostosis disorders, cell proliferative diseases or disorders, or tumor progression associated with the constitutive activation of a receptor protein tyrosine kinase.

The present invention provides novel substituted quinoline compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

The invention relates to processes for preparing compounds having the formula (I) and crystalline forms thereof, wherein Ar is aryl or heteroaryl, L is an optional alkylene linker, and R2, R3, R4, and R5, are as defined in the specification herein, which compounds are useful as kinase inhibitors, in particular, inhibitors of protein tyrosine kinase and p38 kinase.

The invention relates to dermatological compositions of Oxaprozin or a closely related compound suitable adapted for the treatment of a dermatological disease, where at least two of the enzymes selected from protein tyrosine kinase Syk, protein tyrosine kinase ZAP-70 and phosphodiesterase IV play a role in mediating the dermatological disease. The invention also encompasses dermatological compositions for the treatment of pruritus.

The invention relates to processes for preparing compounds having the formula, and crystalline forms thereof, wherein Ar is aryl or heteroaryl, L is an optional alkylene linker, and R2, R3, R4, and R5, are as defined in the specification herein, which compounds are useful as kinase inhibitors, in particular, inhibitors of protein tyrosine kinase and p38 kinase.

The invention relates to processes for preparing compounds having the formula,and crystalline forms thereof, wherein Ar is aryl or heteroaryl, L is an optional alkylene linker, and R2, R3, R4, and R5, are as defined in the specification herein, which compounds are useful as kinase inhibitors, in particular, inhibitors of protein tyrosine kinase and p38 kinase.

The invention relates to processes for preparing compounds having the formula, and crystalline forms thereof, wherein Ar is aryl or heteroaryl, L is an optional alkylene linker, and R2, R3, R4, and R5, are as defined in the specification herein, which compounds are useful as kinase inhibitors, in particular, inhibitors of protein tyrosine kinase and p38 kinase.

Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. The chimeric receptor includes an extracellular portion which is capable of specifically recognizing and binding the target cell or target infective agent, and (b) an intracellular portion of a protein-tyrosine kinase which is capable of signalling the therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.

This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds, compositions and methods for the inhibition of kinase activity. The invention also provides compounds, compositions and methods for treating cell proliferative diseases and conditions.

This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

The present invention relates to methods and compositions for the inhibition of adaptor protein / protein tyrosine kinase protein interactions, especially wherein those interactions involving a protein tyrosine kinase capable of complexing with a member of the SH2-and / or SH3-containing family of adaptor proteins are associated with a cell proliferative disorder. Specifically, the present invention relates to particular compounds, especially quinazoline derivative compounds, and methods utilizing such compounds.

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.

Various thienopyrimidine-based analog compounds are able to selectively inhibit the Src family of tyrosine kinases. These compounds are useful in the treatment of various diseases including hyperproliferative diseases, hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic / immunological diseases, or viral infections.

The present invention relates to methods and compositions designed for treatment, management, or prevention of a hyperproliferative cell disease, particular cancer. The methods of the invention comprise the administration of an effective amount of a composition that targets cells expressing low molecular weight protein tyrosine kinase (“LMW-PTP”) in particular using moieties that bind an Eph family receptor tyrosine kinase, such as EphA2 or EphA4, and inhibits or reduces LMW-PTP expression and / or activity. In one embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety attached to a delivery vehicle, and one or more agents that inhibit LMW-PTP expression and / or activity operatively associated with the delivery vehicle. In another embodiment, the method of the invention comprises administering to a subject a composition comprising a nucleic acid comprising a nucleotide sequence encoding an EphA2 or EphA4 targeting moiety and an agent that inhibits or reduces LMW-PTP expression and / or activity. In yet another embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety and a nucleic acid comprising a nucleotide sequence encoding an agent that inhibits or reduces LMW-PTP expression and / or activity, where the nucleic acid is operatively associated with the delivery vehicle. Pharmaceutical compositions are also provided by the present invention.

The invention relates to quinazoline derivatives having a general formula (I), and mixture of their optically active body or racemic body, and diastereoisomer, their pharmaceutically acceptable salts, hydrate or solvate, wherein R1, R2, A, X and Q1 are defined in the specification. The derivatives can be used for preparing protein tyrosine coyness inhibitor, and for preparing medicament for treating and / or preventing cancer and other hyperplasia diseases.

The present invention provides a method for identifying inhibitors of protein kinases and / or protein phosphatases. Methods are also provided for inhibiting protein kinase and / or protein phosphatase activity. Specific non-peptide protein tyrosine kinase and / or protein phosphatase inhibitors are provided. The protein kinase or protein phosphatase inhibitors of the present invention may be used to treat a number of conditions in patients, including cancer, psoriasis, arthrosclerosis, immune system activity, Type II diabetes, and obesity.

The invention relates to a dicoumarol compound shown in a general formula I, wherein definition of each substituent is described in the specification. The invention also relates to a preparation method of the dicoumarol compound, and application of the dicoumarol compound serving as protein tyrosine kinase inhibitor in the field of tumor resistance.

The invention discloses an EGFR inhibitor. The EGFR inhibitor is of the structure shown in the formula (I) and is a compound including alpha, beta-unsaturated carboxylic acid amides. Meanwhile, the invention discloses a preparing method of the compound and the application of the compound serving as a protein tyrosine kinase inhibitor, especially the inhibiting function on T790M variant EGFR as the EGFR inhibitor, and the application on treating diseases such as the kidney cancer, the ling cancer, the prostate cancer, the pancreatic cancer the breast cancer and the spongiocytoma which are related to EGFR over expression. The structure is shown in the specification.

The present invention relates to thienopyrmidine compounds of formula (I) (one of A1 and A2 is S and the other is CH), salts thereof, as well as use and preparation of the same. These compounds are inhibitors of various protein tyrosine kinases (PTKs) of the ErbB family and consequently are useful in the treatment of disorders mediated by aberrant activity of such kinases.

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 present invention relates to compounds of Formula I or a stereomer, a tautomer, a solvate, a pharmaceutically acceptable salt, or a prodrug thereof, pharmaceutical formulations containing the compounds, methods of treatments using the compounds, for example, protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders and methods of preparing medicaments comprising the compounds.

The invention is directed to aminoquinoline and aminoquinazoline compounds of Formula I: where R1, R2, R3, B, Z, Q, p, q and X are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and / or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and / or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and / or disorders related to FLT3 and / or TrkB. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

The present invention provides a quinazoline compound shown in formula (I), or pharmaceutically acceptable salt thereof. R1, R2 and R7 are independently and respectively selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, halogenate C1-6 alkyl, halogenate C1-6 alkoxy, hydroxyl C1-6 alkyl, hydroxyl C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C3-8 cycloalkyloxy, optional aryl or heteroaryl substituted by R6, nitryl, amino, C1-6 alkylamino, and di(C1-6 alkyl)amino; it comprises at least one C3-8 heterocycloalkyloxy selected from N, O, S heteroatoms; Z is -NR4-, C(R5)2, S or -O-, R4 being hydrogen or C1-3 alkyl, and R5 being selected from hydrogen or C1-3 alkyl; R3 is selected from hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy or halogenate C1-6 alkyl; R6 is selected from hydrogen, C1-3 alkyl, hydroxyl, halogen, C1-3 alkoxy; and n is 0 to 5. The present invention further provides a preparation method of the compound shown in formula (I) or the pharmaceutically acceptable salt and pharmaceutical usage thereof, which can be used as medicines or lead compounds for curing diseases such as tumour and cancer related to protein tyrosine kinase.

This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling. The invention also provides compounds, compositions and methods for treating cell proliferative diseases and conditions and opthalmological diseases, disorders and conditions.

The present invention provides new compounds and methods for treating a disease responsive to inhibition of kinase activity, for example a disease responsive to inhibition of protein tyrosine kinase activity, for example a disease responsive to inhibition of protein tyrosine kinase activity of growth factor receptors, for example a disease responsive to inhibition of receptor type tyrosine kinase signaling, or for example, a disease responsive to inhibition of VEGF receptor signaling.

The invention is directed to aminopyrimidine compounds of Formula I: where R3, B, Z, Q, p, q and R1 are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and / or c-kit and / or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and / or c-kit and / or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and / or disorders related to FLT3 and / or c-kit and / or TrkB. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.