Haematologica Reports 2005; 1(issue 8): 28-31[prev][index][next]

SKI-606 and beyond
Boschelli DH,¹ Boschelli F,² Wu B,¹ Ye F,¹ Wang Y,² Golas JM,² Young T,² Lucas J^2
1Chemical and Screening Sciences,²Oncology, Wyeth Research, 401 N. Middletown Road, Pearl River, NY, 10965, USA

4-Phenylamino-3-quinolinecarbonitriles have been extensively studied by Wyeth as inhibitors of diverse kinases including EGFR, HER-2, and MEK.^1,2 Screening of a library of 4-phenylamino-3-quinolinecarbonitriles with various substituents on the 4-phenylamino group identified 1 as an inhibitor of Src kinase³ (Scheme 1).
Optimization of this screening lead led to SKI-606, currently in clinical trials for the treatment of solid tumors.⁴ Subsequent to the discovery that SKI-606 was a potent Src inhibitor, it was determined that this compound was also a potent inhibitor of Abl kinase.⁵ [>Read full article in PDF]