| Abstract
| - A potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspasemimetic (SM-131, 2) has been designed, synthesized, and evaluated. Compound 2 binds to X-linked inhibitorsof apoptosis proteins (XIAP) with a Ki of 61 nM in a competitive binding assay and directly antagonizesthe XIAP inhibition of caspase-9 activity in a cell-free functional assay. Compound 2 achieves an IC50 of100 nM in inhibition of cell growth and effectively induces cell death in the MDA-MB-231 human breastcancer cell line.
|
