イワサキ　マサユキ   IWASAKI Masayuki   岩崎　正幸    所属   研究施設 研究施設    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Next-generation NAMPT inhibitors identified by sequential high-throughput phenotypic chemical and functional genomic screens.
掲載誌名	正式名：Chemistry & biology 略　 称：Chem Biol ISSNコード：18791301/10745521
掲載区分	国外
巻・号・頁	20(11),pp.1352-63
著者・共著者	Matheny Christina J, Wei Michael C, Bassik Michael C, Donnelly Alicia J, Kampmann Martin, Iwasaki Masayuki, Piloto Obdulio, Solow-Cordero David E, Bouley Donna M, Rau Rachel, Brown Patrick, McManus Michael T, Weissman Jonathan S, Cleary Michael L
発行年月	2013/11
概要	Phenotypic high-throughput chemical screens allow for discovery of small molecules that modulate complex phenotypes and provide lead compounds for novel therapies; however, identification of the mechanistically relevant targets remains a major experimental challenge. We report the application of sequential unbiased high-throughput chemical and ultracomplex small hairpin RNA (shRNA) screens to identify a distinctive class of inhibitors that target nicotinamide phosphoribosyl transferase (NAMPT), a rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide, a crucial cofactor in many biochemical processes. The lead compound STF-118804 is a highly specific NAMPT inhibitor, improves survival in an orthotopic xenotransplant model of high-risk acute lymphoblastic leukemia, and targets leukemia stem cells. Tandem high-throughput screening using chemical and ultracomplex shRNA libraries, therefore, provides a rapid chemical genetics approach for seamless progression from small-molecule lead identification to target discovery and validation.
DOI	10.1016/j.chembiol.2013.09.014
PMID	24183972