Small-Molecule Intervention At The Dimerization Interface Of Survivin By Novel Rigidized Scaffolds

Introduction Survivin is a nodal protein involved in several cellular pathways. It is a member of the IAP family and an integral component of the chromosomal passenger complex, where it binds to borealin and INCENP through its dimerization interface. By targeting survivin with a small molecule at its dimerization interface, inhibition of the proliferation of cancer cells has been suggested. With Abbott 8, a small-molecule dimerization inhibitor has been recently reported. The structure–activity relationship of this series of inhibitors implied that the middle pyridin-2(1H)-one ring did not tolerate modifications of any kind.