Jak/stat pathway inhibitors and the uses thereof

Details Jak/stat pathway inhibitors and the uses thereof Jak/stat pathway inhibitors and the uses thereof

A - Human Necessities

61

K

A61K 31/505 (2006.01) A61K 31/00 (2006.01) A61K 31/517 (2006.01) A61K 31/55 (2006.01) A61P 19/02 (2006.01) A61P 35/00 (2006.01) A61P 35/02 (2006.01) A61P 37/00 (2006.01) A61P 43/00 (2006.01)

Patent

CA 2397774

The role of JAK/STAT signal transduction pathway cellular mechanisms that lead to the onset and progression of degenerative joint diseases or disorders such as osteoarthritis (OA) is disclosed. Certain known effective OA therapeutics such as hymenialdisine, debromohymenialdisine, and its variants and derivatives are shown to function as JAK3-specific inhibitors, which downregulate steady state mRNA levels of key cellular components involved in cartilage degradation. Another JAK3-specific inhibitor, not previously known as an OA therapeutic, is shown to downregulate steady state mRNA levels of various cellular components involved in cartilage degradation in a manner identical to that of the known OA therapeutics.

L'invention concerne le rôle joué par les mécanismes cellulaires du trajet de transduction de signal de JAK/STAT conduisant à l'apparition et à la progression de maladies articulaires dégénératives ou de troubles, tels que l'ostéoarthrite (OA). On démontre que certains agents thérapeutiques efficaces et connus de l'ostéoarthrite (OA), tels que hymenialdisine, débromohymenialdisine, et leurs variantes et dérivés fonctionnent en tant qu'inhibiteurs spécifiques de JAK3, ce qui régule à la baisse les niveaux fixes d'ARNm de constituants cellulaires clé impliqués dans la dégradation des cartilages. On démontre qu'un autre inhibiteur spécifique de JAK3, inconnu précedemment en tant qu'agent thérapeutique de l'ostéoarthrite (OA), régule à la baisse les niveaux fixes d'ARNm de différents constituants cellulaires jouant un rôle dans la dégradation des cartilages de façon identique à celui des agents thérapeutiques connus de l'ostéoarthrite.

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