57 results about "Jnk inhibitor" patented technology

Compounds having activity as selective inhibitors of JNK are disclosed. The compounds of this invention are indazole derivatives having the following structure: wherein R1, R2 and A are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to JNK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

The present invention relates to methods and compositions designed for the treatment, management or prevention of cancer. The methods of the invention comprise the administration of an effective amount of one or more inhibitors of JNK in combination with the administration of an effective amount of one or more other agents useful for cancer therapy. The invention also provides pharmaceutical compositions comprising one or more inhibitors of JNK in combination with one or more other agents useful for cancer therapy. In particular, the invention is directed to methods of treatment and prevention of cancer by the administration of an effective amount of one or more inhibitors of JNK in combination with standard and experimental chemotherapies, hormonal therapies, bone marrow transplants, stem cell replacement therapies, biological therapies/immunotherapies and/or radiation therapies for treatment or prevention of cancer. Also included are methods of treatment of cancer by the administration of one or more inhibitors of JNK in combination with surgery, alone or in further combination with standard and experimental chemotherapies, hormonal therapies, bone marrow transplants, stem cell replacement therapies, biological therapies/immunotherapies and/or radiation therapies.

The present invention provides solid forms of Compound (I), pharmaceutical compositions thereof, and methods for the treatment or prevention of diseases including, but not limited to a liver disease, cancer, a cardiovascular disease, a metabolic disease, a renal disease, an autoimmune condition, an inflammatory condition, macular degeneration, pain and related syndromes, disease-related wasting, an asbestos-related condition, pulmonary hypertension, ischemia/reperfusion injury, central nervous system (CNS) injury/damage or a disease treatable or preventable by the inhibition of JNK. In particular, the invention relates to certain novel crystal forms of the compound 1-(5-(1H-1,2,4-triazol-5-yl)(1H-indazol-3-yl))-3-(2-piperidylethoxy)benzene.

Provided is an isolated human naive pluripotent stem cell (PSC), wherein: (i) when the naive PSC is a female PSC, then said naive female PSC has two unmethylated alleles of an X-inactive specific transcript (XIST) gene; and (ii) when said naive PSC is a male PSC, then said naive male PSC has an unmethylated allele of said XIST gene. Also provided is a culture medium which comprises an ERK1/2 inhibitor, a GSK3beta inhibitor, a p38 inhibitor, a JNK inhibitor, a STAT3 activator and at least one agent selected from the group consisting of: bFGF, TGFbeta 1, a PKC inhibitor, a ROCK inhibitor and a NOTCH inhibitor; or at least agent selected from the group consisting of: a TGFR inhibitor, a FGFR inhibitor, a PKC inhibitor, a ROCK inhibitor and a NOTCH inhibitor.

This invention is generally directed to Indazole Derivatives having the following structure:

or pharmaceutically acceptable salt thereof, wherein R₁, R₂ and A are as defined herein. Such compounds have utility in the treatment of a wide range of diseases and disorders that are responsive to JNK inhibition, such as an inflammatory disease or disorder. Thus, methods of treating such diseases and disorders are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

The present invention relates to methods for treating, preventing, managing and/or modifying pain, comprising administering an effective amount of a JNK Inhibitor to a patient in need thereof. Specific embodiments encompass the administration of a JNK Inhibitor, alone or in combination with a second active agent and/or surgery or physical therapy. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

Compounds having activity as selective inhibitors of JNK are disclosed The compounds of this invention are pyrazoloanthrone and derivatives thereof having the following structure:

wherein R₁ and R₂ are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to JNK inhibition. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

Methods of treating, preventing and/or managing a central nervous system injury/damage and related syndromes are disclosed. Specific methods encompass the administration of a JNK inhibitor alone or in combination with a second active agent. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

Isothiazoloanthrones, isooxazoloanthrones, isoindolanthrones, and derivatives thereof having the general formula: and pharmaceutically acceptable salts thereof, wherein R0 is -CH2-, -SO-, -O-, -SO2-, or -S-; compositions comprising the isothiazoloanthrones, isooxazoloanthrones, isoindolanthrones, and derivatives thereof; and methods for treating or preventing a disorder alleviated by inhibiting Jun N-terminal kinase (JNK) by administering the isothiazoloanthrones, isooxazoloanthrones, isoindolanthrones, and derivatives thereof are described herein.

A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula

wherein ring A and ring B are each an optionally substituted benzene ring, X is —O—, —N═, —NR³— or —CHR³—, R² is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R¹ is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.

The invention discloses a mycobacterium tuberculosis secretory protein PtpA capable of dephosphorylating p-JNK and p-P38, and belongs to the cytobiology field. The invention ascertains the mycobacterium tuberculosis secretory protein PtpA capable of inhibiting two signal pathways of p-JNK and p-P38, and provides a protein, namely ubiquitin, capable of increasing PtpA activity for the first time. The secretory protein PtpA and the ubiquitin can provide novel tools and ideas for treatment of a plurality of clinical diseases, particularly have a broad prospect in aspects of development and clinical applications of a plurality of medicines such as antineoplastic medicines, and other aspects, and can be directly used for the scientific research field or for guiding development of JNK inhibitors and P38 inhibitors. In addition, the secretory protein PtpA and the ubiquitin have important theory meaning for searching new medicine targets and screening new medicines.

The present invention relates to a method for monitoring migration, invasion, and metastasis of cancer cells by observing the shape of cancer cells cultured in a three-dimensional environment and measuring the activity, expression, and changes in expression sites of proteins associated with invadopodia formation and metastasis, and the degradation of an extracellular matrix; and to a method for screening a cancer metastasis inhibitor. More specifically, it was verified that the reduction in c-Jun phosphorylation induced the increase in snail1 and the decrease in cortactin expression in the cells cultured in a three-dimensional environment and the expression regulation relations between the proteins were identical to those in breast cancer tissues obtained from patients. In addition, it was verified that, when breast cancer cells in a three-dimensional collagen gel environment were treated with a JNK inhibitor, the shape of the cells became longer; the contact region of the cells and the extracellular matrix became flattened and thinner; the migration of cancer cells was decreased; and the changes in protein expression was observed, such as the increase in TGFβ1 expression, the increases in smad2 and smad3 expression and activity, the increase in snail1 expression, the decrease in cortactin expression, and the resulting decrease in invadopodia formation. In addition, in a three-dimensional collagen gel environment, MT1-MMP besides the cortactin can be used as a marker of invadopodia, and it was verified that the inhibition of JNK led to the decrease in cortactin expression and the increase in snail1 expression, badly influenced the site and role of MT1-MMP to inhibit the formation of invadopodia, and inhibited the degrading activity of a collagen gel substrate. Thus, the present invention can be used as a method for monitoring migration, invasion, metastasis, and the degree of metastasis of cancer cells and a method for screening a cancer metastasis inhibitor, and will be useful as one of screening methods capable of creating low-cost, high-efficient added value at the time of pre-clinical tests required for drug development.

Methods for treating, preventing and/or managing an asbestos-related disease or disorder are disclosed. Specific embodiments encompass the administration of a JNK Inhibitor, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, clathrate, or prodrug thereof, alone or in combination with a second active agent and/or chemotherapy, surgery, or radiation therapy. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in the methods of the invention are also disclosed.

The invention relates to use of a composition comprising an inhibitor of adenylyl cyclase in the elongation of circadian rhythm, a method of extending the period of circadian rhythm in a subject, said method comprising administering to said subject an inhibitor of adenylyl cyclase, and to adenylyl cyclase inhibitor for use in the treatment of a disorder of the circadian rhythm. Preferably the inhibitor is a P-site inhibitor, preferably 9-(tetrahydrofuryl)-adenine. The composition may further comprise a JNK inhibitor.

The brain specific isoform (JNK3) of c-Jun NH2-terminal kinase (JNK) has been found to mediate the degeneration of spinal motor neurons caused by SMN deficiency in spinal muscular atrophy (SMA). Moreover, the ability of JNK inhibitors to reduce degeneration of neurons lacking SMN is also disclosed. The JNK signaling pathway can therefore mediate neurode-generation in SMA and represents a therapeutic target for treatment of SMA.

This invention relates to the use of a JNK inhibitor for treating and/or preventing skin diseases selected from psoriasis and dermatitis.

The invention discloses an application of a JNK inhibitor in preparing a drug. The medicines are used for preventing and treating fungal infection. The JNK inhibitor, as a gene target drug, is capable of conducting targeted therapy on the fungal infection, and the drug is strong in application and is capable of effectively improving the capacity of a body's immune system to resist the fungal infection, so as to prevent and treat the fungal infection. The JNK inhibitor can enhance the accuracy of fungus treatment from body self, and the JNK inhibitor can effectively prevent the occurrence of drug-resistance bacteria, so that a curative effect of preventing and treating the fungal infection is obviously improved. In addition, the JNK inhibitor, in comparison with existing broad-spectrum anti-fungal drugs, is low in cost and cheap in price, and the JNK inhibitor is relatively high in economic significance and clinical application value.

The invention relates to prodrugs of JNK inhibitors and corresponding methods, formulations, and compositions for inhibiting JNK and treating JNK-mediated disorders. The application discloses prodrugs of JNK inhibitors, as described below in formula I:

wherein m, n, p, q, Q, r, R¹, R², R³, X, X¹, X², X³, X⁴, X⁵, Y¹, Y², Z¹ and Z² areas defined herein. The compounds and compositions disclosed herein are useful to modulate the activity of JNK and treat diseases associated with JNK activity. Disclosed are methods and formulations for inhibiting JNK and treating JNK-mediated disorders, and the like, with the compounds, and processes for making said compounds, and corresponding compositions, disclosed herein.