Methods and Compounds Useful to Induce Apoptosis in Cancer Cells

A method for inducing apoptosis, modulating caspase activity, or inducing cell death in a mammal comprising contacting target cells with a compound having the formula (I)

• wherein:
• each R6, R8, R9, and R10 are independently hydrogen, hydroxyl, —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C1-C6)alkylhalo, —OC(O)(C1-C6)alkyl, or halo;
• each R7 is independently hydrogen, —(C3-C8)cycloalkyl, —(C6-C10)aryl, or —(C1-C6)alkyl(C6-C10)aryl;
• or a pharmaceutically acceptable salt thereof, effective to induce apoptosis, modulate caspase activity, or induce cell death the target cells.

A method of identifying an agent that inhibits the anti-apoptotic activity of the Bcl-2 family proteins comprising:

• (a) identifying a Bcl-2 inhibitor or a labeled Bcl-2 inhibitor, wherein the inhibitor is selected from the group consisting of gossypol, apogossypol, derivatives of apogossypol, theaflavin, theaflavin-3′-gallate, theaflavanin, (−) gallocatechin-3-gallate (GCG), (−) epigallocatechin-3-gallate (EGCG), (−) catechin-3-gallate (CG), (−) epicatechin-3-gallate (ECG), and derivatives of purpurogallin;
• (b) contacting the bound inhibitor with a candidate agent, said candidate agent suspected of being able to inhibit the Bcl-2 family proteins;
• and
• (c) detecting dissociation of the inhibitor from the Bcl-2 family protein, whereby the agent is identified as an agent that inhibits Bcl-2 family proteins.