The present invention provides agents and compositions for modulating the apoptotic state of a cell. The agents comprise derivatives of antimycins which bind to an anti-apoptotic Bcl-2 family member protein. Further, the agents preferentially induce apoptosis in cells that over-express anti-apoptotic Bcl-2 family member proteins and typically exhibit reduced binding affinity for cytochrome B. Pharmaceutical uses of the agents and compositions include treating apoptosis-associated disease, such as neoplasia and drug resistance, are also disclosed.