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

摘要

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