Thursday, November 21, 2013
This week in techniques
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Small molecule target
discovery using forward genetics
In vitro, cell culture and mouse studies suggest a high
hairpin RNA screening platform could be useful for identifying the
targets of lead compounds. A cell culture screen for small molecule
inhibitors of acute lymphoblastic leukemia growth identified STF-11804,
which inhibited tumor growth at nanomolar concentrations in a range
of tumor lines. In a genomewide screen for shRNAs that enhance
STF-118804 activity, shRNA against nicotinamide
phosphoribosyl transferase (NamPRT;
increased STF-118804 sensitivity compared with shRNAs against other targets. In
vitro, STF-118804 inhibited NAMPT activity. Next steps include
optimization and preclinical development of STF-118804 for hematological
Published online Nov. 21, 2013
Stanford University has pending patents on STF-118804; University
of California has filed patents on use of its shRNA
screening platform for target identification; both sets of patents available
Mattheny, C.J. et al.
Chem. Biol.; published online Oct. 31, 2013;
Contact: Michael L. Cleary, Stanford University School of
Medicine, Stanford, Calif.
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