IAP E3 LIGASE DIRECTED PROTEOLYSIS TARGETING CHIMERIC MOLECULES

摘要

Proteolysis Targeting Chimeric molecules (Protacs) are bifunctional molecules which which can simultaneously bind a target protein and an E3 ubiquitin ligase thereby bringing the ligase and target in close proximity These bifunctional molecules allow the efficient ubiquitin transfer from the ligase complex to the target protein which is subsequently recognized by the proteasome and degraded. This degradation of the target protein provides treatment of diseases or conditions modulated through the target protein by effectively lowering the level of said target protein in the cells of the patient. The present invention provides Protac compounds incorporating a selective E3 Ligase IAP binding moiety (IAP binding moiety) as the degradation component, functioning to recruit target proteins to the E3 ubiquitin ligase IAP for degradation.