1214265-78-7Relevant articles and documents
Structure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors
Kiryanov, Andre,Natala, Srinivasa,Jones, Benjamin,McBride, Christopher,Feher, Victoria,Lam, Betty,Liu, Yan,Honda, Kouhei,Uchiyama, Noriko,Kawamoto, Tomohiro,Hikichi, Yuichi,Zhang, Lilly,Hosfield, David,Skene, Robert,Zou, Hua,Stafford, Jeffrey,Cao, Xiaodong,Ichikawa, Takashi
, p. 1311 - 1315 (2017/06/21)
Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]pteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits >7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model.