31 results about "C-Jun N-terminal kinases" patented technology

The present invention provide a compound of formula I or II:

or a pharmaceutically acceptable derivative thereof, wherein R¹, R², R³, and R⁴ are as described in the specification. These compounds are inhibitors of protein kinase, particularly inhibitors of JNK, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli; and Src-family kinases, especially Src and Lck kinases. These compounds are also inhibitors of GSK3 and CDK2 kinases. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

The present invention relates to compounds that are inhibitors of c-jun N-terminal kinase 1, 2, or 3 (JNK1, JNK2, or JNK3), compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders regulated by the activation of JNK1, JNK2 and JNK3.

The compound represented by the general formula (I):

• • wherein, a fused ring AB represents a 5- to 10-membered fused heterocyclic ring; R¹ represents (1) a hydrogen atom, (2) a halogen atom, (3) a cyano group, (4) an oxo group, (5) an optionally protected hydroxyl group, (6) an optionally protected carboxyl group, (7) an optionally protected amino group, (8) a cyclic group which may have a substituent (s), (9) an aliphatic hydrocarbon group which may have a substituent (s), or (10) an optionally protected thiol group; n represents 0 or an integer of 1 to 8; provided that n represents an integer of not less than 2, plural R¹ are the same or different; a salt thereof, a solvate thereof or a prodrug thereof has a kinase (especially c-Jun N-terminal kinase) inhibitory activity and an inhibitory activity of a function of AP-1 as a transcription factor, it is useful as a preventive and/or therapeutic agent for a for example, a diabetes of metabolic disease, etc., a rheumatoid arthritis of inflammatory, etc.

The present invention provides novel compounds according to Formula (I): where Ring A, Ring B, X, L₁, L₂, R^A, R^C, R^D, R^E, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.

Extracts of Lycium barbarum serve as a neuroprotective agent against β-amyloid peptide neurotoxicity which thus permits their use for the treatment of Alzheimer's disease (AD) and for the prevention of neuronal loss in aging against the accumulation of β-amyloid peptide in the brain. Stress kinases (c-Jun N-terminal kinase and double-stranded RNA-dependent protein kinase) are used as a technological platform for screening neuroprotective drugs.

Methods of reducing Wallerian degeneration are disclosed. These methods comprise inhibiting expression or activity of a mixed lineage kinas such as a dual leucine-zipper-bearing kinase (DLK), inhibiting expression or activity of a molecule acting downstream from DLK, such as a c-Jun N-terminal kinase (JNK), or a combination thereof. Further disclosed are methods of screening candidate compounds for DLK inhibition activity. These methods comprise providing a neuronal culture comprising a plurality of axons; contacting the culture with a candidate compound and with an axon degeneration-triggering agent; and comparing axonal degeneration in the culture to a control culture comprising the axon degeneration-triggering agent but not the candidate compound.

The present invention is based at least in part on the discovery of a role for the JNK signaling pathway in longevity. In particular, the present inventors have shown that overexpression of c-jun N-terminal kinase 1 (jnk-1) extends lifespan and that said extended lifespan is associated with DAF-16 phosphorylation by JNK-1 and the consequent DAF-16 localization to the nucleus. Accordingly, the present invention features methods of identifying modulators of longevity in assays featuring organisms and/or cells having a JNK signaling pathway and, optionally, an IR signaling pathway. Also featured is an in vitro method of identifying an agent capable of enhancing longevity featuring an assay composition having a JNK signaling pathway molecule and insulin signaling pathway molecule. Further featured are therapeutic methods for the use of JNK signaling pathway modulators to enhance longevity, to prevent or reduce obesity and to prevent or treat type II diabetes.

The invention relates to pharmaceutical compositions and methods for treating Meniére's Disease. In particular, the invention provides a method for treating Meniére's Disease in a subject in need thereof by administering a pharmaceutical composition comprising a peptide inhibitor of c-Jun N-terminal kinase.

A method for controlling circadian rhythm disorders is described, characterized by inhibiting the phosphorylation of BMAL1 by c-Jun N-terminal kinase 3 (JNK3) due to the interaction between JNK3 and BMAL1; a method for preventing and/or treating diseases caused by circadian rhythm disorders; and a method for identifying a compound that inhibit phosphorylation of BMAL1 by JNK3. Also provided are: an agent for controlling circadian rhythm disorders, having the above characteristics; an agent for treating and/or preventing diseases caused by circadian rhythm disorders; a compound obtained by the identification method described above; an agent for inhibiting the phosphorylation of BMAL1 by JNK3, containing the compound; an agent for recovering the suppressed transcriptional activity of the complexes containing BMAL1 and CLOCK and for inhibiting the phosphorylation the same, containing an agent for inhibiting the expression and/or function of JNK3; and a pharmaceutical composition containing one of these.

The invention relates to pharmaceutical compositions and methods for treating inner ear disorders. In particular, the invention provides a method for treating and/or preventing acute inner ear tinnitus in a subject in need thereof by administering a pharmaceutical composition comprising a peptide inhibitor of c-Jun N-terminal kinase.

The invention relates to an anti-inflammatory application of pomegranate flower polyphenol. An enzyme-linked immunosorbent assay (ELISA) technology is adopted to analyze the influence of pomegranate flower polyphenol on the lipopolysaccharide-induced inflammatory response of mouse macrophage (RAW264.7), and the results show that pomegranate flower polyphenol can prominently inhibit the excess releasing of inflammatory mediator namely nitrogen monoxide (NO) and excess secretion of inflammation inhibiting factor namely interleukin 6, interleukin 1[beta], and tumor necrosis factor [alpha]. The western blotting shows that pomegranate flower polyphenol can inhibit the excess expression of the following three key enzymes in the inflammation signal path: extracelluar regulated protein kinase, C-JUN N-terminal kinase, and epoxidase 2. So the pomegranate flower polyphenol has a very good anti-inflammatory activity, can be used as the lead compound of anti-inflammatory drugs to prevent or treat inflammation caused by excess of nitrogen monoxide (NO), tumor necrosis factor [alpha] (TNF-[alpha]), interleukin 6 (IL-6) or interleukin 1[beta] (IL-1[beta]).

The present invention relates to sulfonamide derivatives of formula I notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such sulfonamide derivatives. Said sulfonamide derivatives are useful in the treatment of neuronal disorders, autoimmune diseases, cancer and cardiovascular diseases. Furthermore, said sulfonamide derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK2 and -3. The present invention is furthermore related to novel sulfonamide derivatives as well as to methods of their preparation.

The invention discloses application of a CTSG (cathepsin G) cell factor in the preparation of medicaments to treat hepatic failure. Death of mass hepatic cells occurs during the course of hepatic failure; the CTSG cell factor helps overcome the aforementioned problem. CTSG JNK (c-Jun N-terminal kinase) is one of MAPK (mitogen-activated protein kinase) family members; JNK pathway can inhibit apoptosis of hepatic cells by regulating the expression of CTSG. The CTSG cell factor can be applied to the preparation of medicaments to treat hepatic failure to significantly increase biochemical indexesof a patient, reduce bilirubin level, lower aminotransferase, improve the coagulation function, inhibit cell apoptosis, promote the regeneration of hepatic cells and bile duct cells, prevent occurrence of fatal complications, such as massive alimentary tract bleeding, severe hepatic encephalopathy and hepatorenal syndrome, extend the survival time of the patient significantly, and increase the survival rate.

The invention relates to the technical field of biology, in particular to a human JNK1 (c-Jun N-terminal kinase) gene targeting small interfering RNA (ribonucleic acid) and application thereof. The small interfering RNA comprises a sense strand and an anti-sense strand, a nucleotide sequence of the sense strand is as shown in SEQ ID NO:2, and a nucleotide sequence of the anti-sense strand is as shown in SEQ ID NO:3. The sequences of the small interfering RNA are not publically reported yet, interference after transcription of the JNK1 gene can be realized to reduce expression of p-JNK in inflamed dental pulp stem cells, apoptosis of the dental pulp stem cells can be specifically reduced, odontoblast differentiation of the dental pulp stem cells is promoted, and a novel treatment scheme is provided for pulpitis.

Endophilin I is a brain-specific protein functioning in clathrin-mediated endocytosis. The present invention is based on the finding that the rat germinal center kinase-like kinase (rGLK), a member of the germinal center kinase (GCK) family of c-jun N-terminal kinase (JNK) activating enzymes, is a novel endophilin I-binding partner. In a first aspect of the present invention, the novel interaction between endophilin I and rGLK is put to use in a novel screening assay. In a second aspect of the present invention, the interaction between endophilin I and GLK is modulated for therapeutic purposes, namely for the prevention and/or curtailment of neurological disorders associated with the JNK pathway. JNK-mediated neuronal cell death is believed to play an important role in injuries and diseases involving neuronal degeneration, such as Huntington's disease.