Dimeric iap inhibitors

Details Dimeric iap inhibitors Dimeric iap inhibitors

C - Chemistry, Metallurgy

07

D

C07D 209/20 (2006.01) A61K 31/40 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2598995

Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inbhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.

L'invention concerne des analogues moléculaires de Smac permettant de moduler une apoptose par leur interaction avec des IAP cellulaires (inhibiteurs de protéines d'apoptose). Ces analogues ont pour base un monomère ou un dimère du tétrapeptide N-terminal de protéines se liant à IAP, notamment Smac/DIABLO, Hid, Grim et Reaper qui interagissent avec une rainure de surface spécifique d'IAP. L'invention concerne également des méthodes d'utilisation de ces analogues peptidiques pour des applications thérapeutiques. Dans des modes de réalisation variés de l'invention, les analogues Smac de l'invention sont combinés à des agents chimiothérapeutiques comprenant de manière non exhaustive des inhibiteurs de topoisomérases, des inhibiteurs de kinases, des NSAID, des taxanes et des composés contenant du platine.

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