286 results about "Protein kinase C iota" patented technology

The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides appropriately functionalized 5,6-fused bicyclics which inhibit, regulate and / or modulate kinase receptor, particularly c-Met, KDR, and flt-3, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions.

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula I:or a pharmaceutically acceptable salt, wherein the variables are as defined herein.Moreover, The compounds of this invention have formula I-A:or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of protein and / or checkpoint kinases, methods of preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of preparing pharmaceutical formulations including one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the protein or checkpoint kinases using such compounds or pharmaceutical compositions.

The present invention relates to chemical compounds having a general formula Iwherein A1, A2, C1, C2, D, L1, L2, Z and R1-8 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.

The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wildtype Abl. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and / or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein, V is NR1R1a, or O—R1, wherein X is H, halo, C1-C6 alkyl, NO2, mono-, di-, or tri-halo substituted methyl, NR13R,14. C(O)O—C1-C6 alkyl, or N(R13)—C(O)—C1-C6 alkyl; Y is H, halo, OH, C1-C6 alkyl, C0-C6alkyl-NR,15R16, NR15R,6, C1-C6 alkoxy, —N(R13)—(CH2)n-NR15R16, —C(O)O—C1-C6 alkyl, —O—(CH2)n—NR15R16, —C(O)—C1-C6 alkyl, —C0-C6-alkyl-R21, —O—R21, —C(O)—R21, —O—(CH2)n—R21, —C(O)—NR13R14, —C(O)—N(R13)-aryl, —C(O)—N(R13)(CH2)n—NR15R16, —C(O)—N(R13)—(CH2)n-aryl —C(O)—N(R13)—(CH2)n-heterocyclyl; or X and Y together with the atoms to which they are attached form a 4-7 membered heterocyclyl or heteroaryl group containing one or two heteroatoms independently selected from O, N, and S. Z is H, NR2R3, —S—R2a, or —O—R2a

Compounds of the formula and pharmaceutically acceptable salts thereof, wherein Q1 and R1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and / or prevention of various diseases and conditions that respond to treatment by inhibition of tyrosine kinases.

This invention relates to 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors. Particular 4-substituted 7-aza-indolin-2-ones disclosed herein are of Formula 1 and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R1, R2, R3, R4, X, Y, and Z are defined herein. The invention fuirther relates to pharmaceutical compositions and dosage forms comprising compounds of Formula 1 and to methods of their use for the treatment and / or prevention of diseases such as, but not limited to, cancer.

The present invention relates to the treatment of oncological, chronic inflammatory and similar diseases with the aid of new families of chemical compounds having improved efficiency with regard to the inhibition of Abl kinase and mutant forms thereof, as well as other therapeutically significant kinases. It describes protein kinase inhibitors in the form of compounds of general formula (I) and compounds of general formula (II), or a tautomer, an individual isomer, a mixture of isomers, a pharmaceutically acceptable salt, a solvate or a hydrate thereof.

The present invention relates to chemical compounds having a general formula I wherein A1, A2, C1, C2, D, L1, L2, Z and R1- are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.

The present invention relates to compounds of the following formula (I) and / or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus also includes the preparation of compounds of formula (I), their uses, in particular in the inhibition of protein kinases which are implicated for example in numerous diseases such as cancers or immune system disorders.

The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A1, A2, A3, A4, R1 and R2 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

A novel agent for therapy and / or prevention of kidney diseases as well as a diagnostic method (detection method) of kidney diseases is disclosed. The agent for therapy and / or prevention of kidney diseases comprises as an effective ingredient a substance which inhibits casein kinase 2. The diagnostic method of kidney diseases according to the present invention comprises measuring activity or content of casein kinase 2, or measuring expression amount of casein kinase 2 gene in a sample separated from body.

The described invention provides compositions, dressings and methods for treating a cutaneous scar in a subject. The compositions of the derived invention contains a pharmaceutical composition comprising a therapeutic amount of a Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) inhibitor comprising an MK2 polypeptide inhibitor or a functional equivalent thereof, and a pharmaceutically acceptable carrier.

There are provided compounds of formula I,wherein:Y represents NR2R3;one of R2 and R3 represents —[C2-4 alkylene-O]1-12—[C2-4 alkylene]-R2a and the other of R2 and R3 has a meaning given in the description; andR, R1, R2a, 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.

A method of inhibiting angiogenesis in a mammal is disclosed, which employs a pharmaceutically acceptable composition containing a selective inhibitor of protein kinase CK2 (also known as casein kinase II) enzymatic activity, such as emodin, aloe-emodin, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), and 4,5,6,7-tetrabromobenzotriazole (TBB). Also disclosed is a use of a selective inhibitor of protein kinase CK2 enzymatic activity in the manufacture of a medicament for inhibiting angiogenesis. An in vitro method of screening a potential antiangiogenic agent is also disclosed. A kit for the treatment of a disease by inhibiting angiogenesis is disclosed that contains the pharmaceutically acceptable composition containing a selective inhibitor of protein kinase CK2 enzymatic activity.

The present invention relates to chemical compounds having a general formula Iwherein A, B, C1, C2, D, L1, L2 and R3-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Tie-2 and Aurora kinase enzymes thereby influencing angiogenesis and the process of cell cycle and cell proliferation, respectively, to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of various protein kinases.

The present invention provides a compound of formula I:or a pharmaceutically acceptable derivative thereof. These compounds are inhibitors of protein kinases, particularly inhibitors of GSK3 mammalian protein kinase. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders.

The invention relates to a combination of treatments, more particularly a combination treatment for HIV-1 infection. The present invention is directed to the use of bryostatin-1 and their natural and synthetic derivatives for AIDS therapy, in particular to the use of bryostatins in combination with other active drugs such as Histone Deacetylases (HDACs) inhibitors and anti-retrovirals, for the treatment of HIV-1 latency. According to the present invention, we provide a combination therapy for the treatment of HIV-1 latency which employs bryostatin-1 (and analogues) and one of the following HDAC inhibitors; valproic acid, butyrate derivatives, hydroxamic acids and benzamides. While HDACi can be used in continuous dosing protocol, bryostatins can be used following a cyclical dosing protocol. Bryostatins can be formulated in pharmaceutical acceptable carriers including nanoparticles, phospholipids nanosomes and / or biodegradable polymer nanospheres. This combination therapy needs to be used in patients treated with antiretroviral therapy (HIV-1 protease inhibitors, HIV-1 reverse transcriptase inhibitors, HIV-1 integrase inhibitors, CCR5 co-receptor inhibitors and fusion inhibitors).

The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of an anti-cancer agent and an IGF1R inhibitor compound of Formula I combination, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The IGF1R inhibitor is represented by Formula I: wherein X1, X2, X3, X4, X5, X6, X7, R1, and Q1 are defined herein.

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula I:or a pharmaceutically acceptable salt, wherein the variables R1, R2, R3, and R4 are as defined herein.

A method for managing withdrawal from an addictive substance is described. The method involves administering one or more peptides having specific activity for the ε and / or γ isozyme of protein kinase C (PKC). The peptide(s) can be administered prior to, concurrent with, or subsequent to administration of the addictive substance. Also described is a kit having at least one container containing a peptide having isozyme-specific activity for εPKC or γPKC and instructions for use.

PCT No. PCT / JP97 / 02609 Sec. 371 Date Mar. 24, 1998 Sec. 102(e) Date Mar. 24, 1998 PCT Filed Jul. 29, 1997 PCT Pub. No. WO98 / 04536 PCT Pub. Date Feb. 5, 1998A thiazole compound of the formula: wherein T is lower alkylene; u is 0 or 1; R1 and R2 are the same or different and are each H, or lower alkyl, etc.; R3 is R4 is H or lower alkanoyloxy-lower alkyl, which shows inhibitory activity on protein kinase C (PKC, Ca2+ / phospholipid-depending serine / threonine protein phosphatase), and are useful as a protein kinase C inhibitor.

The present invention provides inhibitors of protein kinases comprising a molecule having at least a first moiety competent for penetration of the molecule into cells, and a second moiety for having a protein kinase inhibiting effect within the cells. The first moiety is joined to the second moiety through a linker or a spacer. The complex molecules are preferably peptide conjugates having improved cell-permeability, serum stability and kinase selectivity compared to known protein kinase inhibitors. Pharmaceutical compositions that include these protein kinase inhibitors, and methods of using such compositions for treatment of cancers and other diseases associated with protein kinase activity are also disclosed.

There is provided a compound of formula I,which compound has 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, e.g., Src and Lck) and has use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a] pyrimidine compounds as inhibitors of protein and / or checkpoint kinases, methods of preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of preparing pharmaceutical formulations including one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the protein or checkpoint kinases using such compounds or pharmaceutical compositions.

The present invention is directed to compounds of formula I-II and pharmaceutically acceptable tautomers, salts, or stereoisomers thereof which are inhibitors of syk and / or JAK kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition syk and / or JAK kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by syk and / or JAK kinase activity, such as cardiovascular disease, inflammatory disease, autoimmune disease and cell proliferative disorder, thrombosis, allergy, asthma, rheumatoid arthritis, leukemia, or non-Hodgkin's lymphoma. The formula I-II is shown in the description.

The present invention relates to compositions comprising a combination of PKC activators and PKC inhibitors and methods to modulate α-secretase activity; improve or enhance cognitive ability; and / or reduce neurodegeneration in individuals suffering from diseases that impair cognitive ability, particularly Alzheimer's Disease. The invention also relates to methods for improving or enhancing cognitive ability. The present invention also provides methods for increasing the generation of non-amyloidogenic soluble APP (sAPP) comprising the activation of protein kinase C (PKC) in the brain and inhibiting PKC in peripheral tissues. Macrocyclic lactones (i.e. bryostatin class and neristatin class) are preferred PKC activators and Vitamin E is a preferred PKC inhibitor for use in the inventive composition.