Bcl-2-related proteins as drug targets.
The Bcl-2 family of proteins provide the most unambiguous link between mitochondrial functions and apoptosis, as their only (or principal) functions appear to be as regulators of this cell death pathway. Rational drug design to manipulate the functions of these proteins has been hampered by the lack of a clear understanding of a biochemical or molecular function, with disruption of intra-family protein-protein interactions as the only known, but daunting, objective. There has been substantial progress in this task using molecular modeling and drug leads. The prospects are also good for development of chemical tools for functional analysis of the Bcl-2 proteins.
O'Neill
Jason W
JW
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Hockenbery
David M
DM
D000818:Animals; D000968:Antimycin A / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology; D001578:Benzopyrans / Q000378:metabolism / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D008958:Models, Molecular; D009570:Nitriles / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology
D001549:Benzamides; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D007473:Ion Channels; D009570:Nitriles; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D013844:Thiazoles; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D000968:Antimycin A; D045304:Cytochromes c