30 results about "JNK Pathway" patented technology

Compounds having activity as inhibitors of the JNK pathway are disclosed. The compounds of this invention are anilinopyrimidine derivatives having the following structure:wherein R1 through R6 are as defined herein. Such compounds have utility in the treatment of a wide range of conditions that are responsive to inhibition of the JNK pathway. Thus, methods of treating such conditions are also disclosed, as are pharmaceutical compositions containing one or more compounds of the above compounds.

This invention relates to methods for promoting neuronal survival and regeneration using LINGO-1 antagonists and TrkB agonists. Additionally, the invention relates to methods for treating pressure induced optic neuropathies using LINGO-1 antagonists. The invention also relates generally to methods for increasing TrkB activity and inhibiting JNK pathway signaling using a LINGO-1 antagonist.

Provided herein are Aminopurine Compounds having the following structure: (I) wherein R<1 >, R<2> and and R<3> are as defined herein, compositions comprising an effective amount of an Aminopurine Compound and methods for treating or preventing cancer, a cardiovascular disease, a renal disease, an autoimmune condition, an inflammatory condition, macular degeneration, ischemia-reperfusion injury, pain and related syndromes, disease-related wasting, an asbestos-related condition, pulmonary hypertension or a condition treatable or preventable by inhibition of the JNK pathway comprising administering an effective amount of an Aminopurine Compound to a patient in need thereof.

The present invention relates to benzsulfonamide derivatives of formula I and methods of use thereof. The benzsulfonamide derivatives of the present invention are efficient modulators of the JNK pathway. In particular the benzsulfonamide derivatives of the present invention are selective inhibitors of JNK 2 and 3.

Methods of reducing Wallerian degeneration are disclosed. These methods comprise inhibiting expression or activity of a mixed lineage kinase 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.

This invention relates to methods for promoting neuronal survival and regeneration using LINGO-1 antagonists and TrkB agonists. Additionally, the invention relates to methods for treating pressure induced optic neuropathies using LINGO-1 antagonists. The invention also relates generally to methods for increasing TrkB activity and inhibiting JNK pathway signaling using a LINGO-1 antagonist.

The invention belongs to the field of biological medicines and relates to a serum-free medium for mesenchymal stem cells. The serum-free medium provided by the invention comprises a basic medium and additive components, wherein the additive components comprise a JNK pathway inhibitor, an ERK1 / 2 pathway inhibitor, a P38MAPK pathway inhibitor and aminoethanol; the JNK pathway inhibitor comprises but is not limited to SP600125; the ERK1 / 2 pathway inhibitor comprises but is not limited to PD0325901; and the P38MAPK pathway inhibitor comprises at least one of SB202190, SB203580 and BIRB796. The medium for mesenchymal stem cells disclosed by the invention does not contain FBS and does not contain any heterologous animal-derived component, the probability of cell contamination is reduced, and an effect of promoting MSC amplification is achieved.

The present invention is related to sulfonamide derivatives of formula (I0 notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such sulfonamide derivatives. Said sulfonamide derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK 2 and 3. The present invention is furthermore related to novel sulfonamide derivatives as well as to methods of their preparation. The compounds of formula (I) according to the present invention being suitable pharmaceutical agents are those wherein Ar1 and Ar2 are independently from each other substituted or unsubstituted aryl or heteroaryl groups, X is O or S, preferably O; R1 is hydrogen or a C1-C6-alkyl group, or R1 forms a substituted or unsubstituted 5-6 membered saturated or unsaturated ring with Ar1; n is an integer from 0 to 5, preferably between 1-3 and most preferred 1; Y within formula (I) is an unsubstituted or a substituted 4-12-membered saturated cyclic or bicyclic alkyl containing at least one nitrogen atom, whereby one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula (I) thus providing a sulfonamide.

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. Formula (I) IAr1 is a substituted or unsubstituted aryl or heteroaryl group; X is O or S, preferably O; Ar2 a substituted or unsubstituted arylene or heteroarylene group; R1 and R2 are independently selected from the group consisting of hydrogen and a C1-C6-alkyl group.

The present invention is related to benzazole derivatives notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such benzazole derivatives. Said benzazole derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK2 and / or 3. The present invention is furthermore related to novel benzazole derivatives as well as to methods of their preparation. X is O, S or NR0, with R0 being H or an unsubstituted or substituted C1-C6 alkyl; G is an unsubstituted or substituted pyrimidinyl group.

The present invention relates to a pharmaceutical composition, including inhibitors for expression or activity of TIP41 protein, for prevention and treatment of cancer. When the liver cancer cell lines, showing resistance to TRAIL, are treated with TIP41 siRNA and TRAIL, apoptosis is induced in cancer cell. The same effect is found in cases of lung cancer and colon cancer with resistance against TRAIL. Moreover, this induction of apoptosis by TIP41 siRNA and TRAIL was confirmed in tumor xenograft, which was injected with Huh7 liver cancer cells and then was subjected to TIP41 siRNA transfection and TRAIL treatment. In addition, it was confirmed through animal experiments in which the tumor size has reduced and apoptosis was induced by treatment with TIP41 siRNA and TRAIL. Of note, MKK7 / JNK pathway was confirmed to mediate the apoptosis induced by the application of TIP41 siRNA and TRAIL. The apoptosis were verified to be caused by the activation of MKK7 / JNK signaling pathway. Taken together, the present invention provide the strong evidence that the pharmaceutical composition, including inhibitors for TIP41 expression or activity can be used for cancer prevention and treatment as well as an anti-cancer adjuvant. Taken together, the pharmaceutical composition comprising inhibitors for expression or activity of TIP41 protein may be used for prevention and treatment of cancer or as an anti-cancer adjuvant.

The present invention discloses the application of miR-127 inhibitor in the preparation of anti-inflammation and lung injury protection medicine. Inhibition of miR‑127 is effective in preventing lung inflammation and injury induced by lung injury. Inhibitors of miR-127 can reduce the production of pro-inflammatory factors, weaken the inflammatory response of the airway, and reduce the infiltration of inflammatory cells. The present invention discloses that miR-127 inhibitors can be used to prepare medicines for preventing acute lung injury and its complications, and the action mechanism of miR-127 inhibitors for preventing acute lung injury and its complications. The miR-127 inhibitor targets Bcl6 and inhibits LPS-induced inflammatory response by regulating the Bcl6 / Dusp1 / JNK pathway.

The present invention is related to sulfonamide derivatives having a lipophilic moiety and which are substantially soluble. Said compounds are notably for use as pharmaceutically active compounds. The present invention also related to pharmaceutical formulations containing such sulfonamide derivatives. Said sulfonamide derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK 2 and 3. The present invention is furthermore related to novel sulfonamide derivatives as well as to methods of their preparation. The compounds of formula (I) according to the present invention being suitable pharmaceutical agents are those wherein Ar1 and Ar2 are independently from each other substituted or unsubstituted aryl or heteroaryl groups, X is O or S, preferably O;R1 is hydrogen or a C1-C6-alkyl group, or R1 forms a substituted or unsubstituted 5-6-membered saturated or unsaturated ring with Ar1;n is an integer from 0 to 5, preferably between 1-3 and most preferred 1;Y within formula (I) is an unsubstituted or a substituted 4-12-membered saturated cyclic or bicyclic alkyl which is substituted with at least one ionisable moiety to which a lipophilic chain is attached and which is containing at least one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula (I) thus providing a sulfonamide.