Dimeric small molecule potentiators of apoptosis

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 249/04 (2006.01) A61K 31/41 (2006.01) A61K 31/42 (2006.01) C07D 257/04 (2006.01) C07D 263/08 (2006.01)

Patent

CA 2582734

Caspase activity and apoptosis are promoted using active, dimeric Smac peptide mimetics of the general formula M1-L-M2, wherein moieties M1 and M2 are monomeric Smac mimetics and L is a covalent linker. Target cancerous or inflammatory cells are contacted with an effective amount of an active, dimeric Smac mimetic, and a resultant increase in apoptosis of the target cells is detected. The contacting step may be effected by administering to a pharmaceutical composition comprising a therapeutically effective amount of the dimeric mimetic, wherein the individual may be subject to concurrent or antecedent radiation or chemotherapy for treatment of a neoproliferative pathology.

Selon l'invention, l'activité caspase et l'apoptose sont induites à l'aide de mimétiques de peptides Smac dimères de formule générale (M1-L-M2), dans laquelle les fragments M1 et M2 sont des mimétiques Smac monomères, et L est un lieur covalent. Des cellules cancéreuses ou inflammatoires cibles sont placées au contact d'une quantité efficace d'un mimétique Smac dimère, et une augmentation consécutive de l'apoptose des cellules cibles est détectée. L'étape de mise en contact peut être effectuée par administration à un individu d'une composition pharmaceutique contenant une quantité thérapeutiquement efficace du mimétique dimère, ledit individu pouvant être soumis à un rayonnement ou une chimiothérapie concurrent(e) ou antécédent(e) destiné(e) à traiter une pathologie néoproliférative.

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