Identification of a small-molecule inhibitor of class Ia PI3Ks with cell-based screening |
| |
Authors: | Yang Jiong Shamji Alykhan Matchacheep Sirinya Schreiber Stuart L |
| |
Institution: | Howard Hughes Medical Institute, Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA. |
| |
Abstract: | The mammalian target of rapamycin (mTOR) signaling network is central to the regulation of cell growth in response to both growth factors and nutrients. We developed a high-throughput, cell-based assay to identify small-molecule modulators of the mTOR signaling network. One such compound, which we name quinostatin, potently inhibits this network by directly targeting the lipid-kinase activity of the catalytic subunits of class Ia PI3Ks. This study illustrates the power of unbiased, phenotypic screening as a means for illuminating cell circuitry, and resulted in the identification of a chemotype for selective inhibition of the class Ia PI3Ks. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|