Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of polo-like kinase 1 (MLN0905)
This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.
Duffey, Matthew O.,Vos, Tricia J.,Adams, Ruth,Alley, Jennifer,Anthony, Justin,Barrett, Cynthia,Bharathan, Indu,Bowman, Douglas,Bump, Nancy J.,Chau, Ryan,Cullis, Courtney,Driscoll, Denise L.,Elder, Amy,Forsyth, Nancy,Frazer, Jonathan,Guo, Jianping,Guo, Luyi,Hyer, Marc L.,Janowick, David,Kulkarni, Bheemashankar,Lai, Su-Jen,Lasky, Kerri,Li, Gang,Li, Jing,Liao, Debra,Little, Jeremy,Peng, Bo,Qian, Mark G.,Reynolds, Dominic J.,Rezaei, Mansoureh,Scott, Margaret Porter,Sells, Todd B.,Shinde, Vaishali,Shi, Qiuju Judy,Sintchak, Michael D.,Soucy, Francois,Sprott, Kevin T.,Stroud, Stephen G.,Nestor, Michelle,Visiers, Irache,Weatherhead, Gabriel,Ye, Yingchun,Damore, Natalie
supporting information; experimental part
p. 197 - 208
(2012/03/10)
More Articles about upstream products of 1351438-85-1