Thursday, November 7, 2013
U.S. researchers have used forward
genetics, a combination of phenotypic screening and genetics, to identify a
therapeutic for leukemia and its target, the metabolic enzyme nicotinamide phosphoribosyl transferase.1 The platform plugs a gap in phenotypic
screens that typically leave users guessing how their molecules work.
The team started with a target-agnostic
phenotypic screen of 115,000 molecules from a commercial library to identify
compounds that prevented growth of cultured acute lymphoblastic leukemia (ALL)
cells at nanomolar concentrations. The most potent compound, STF-118804,
decreased growth in a variety of ALL cell lines compared with
Amped about NAMPT
Despite the elegant proof of concept
for matching a compound to its target, it is unclear whether STF-1189804 is a
good drug candidate or even whether NAMPT is a viable target.
Osherovich, L. SciBX 6(43); doi:10.1038/scibx.2013.1213 Published online
Nov. 7, 2013
1. Matheny, C.J. et al. Chem. Biol.; published
online Oct. 31, 2013; doi:10.1016/j.chembiol.2013.09.014 Contact: Michael L. Cleary, Stanford
University School of Medicine, Stanford, Calif. e-mail: firstname.lastname@example.org
P. et al. Clin. Cancer Res. 8, 2843-2850 (2002)
D.S. et al. Clin. Cancer Res.; published online Oct. 4, 2013; doi:10.1158/1078-0432.CCR-13-1186
COMPANIES AND INSTITUTIONS MENTIONED
Forma Therapeutics Holdings LLC, Watertown, Mass.
Genentech Inc., South San Francisco, Calif.
Howard Hughes Medical Institute, Chevy Chase, Md.
Roche (SIX:ROG; OTCQX:RHHBY), Basel, Switzerland
Stanford University, Stanford, Calif.
Stanford University School of Medicine, Stanford, Calif.
Topotarget A/S (CSE:TOPO), Copenhagen, Denmark
University of California, San Francisco, Calif.