CHEMICAL MODULATORS OF PRO-APOPTOTIC BAX AND BCL-2 POLYPEPTIDES

摘要

The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 family polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an ±1 helix, ±2 helix, a loop between ±1-±2, ±6 helix, and select residues of ±4, ±5, and ±8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta-loop, or combination thereof.