| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1370510 | Bioorganic & Medicinal Chemistry Letters | 2015 | 6 Pages |
Abstract
Based on a putative binding mode of quizartinib (AC220, 1), a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor in Phase III clinical development, we have designed de novo a simpler aminopyridine-based hinge binding motif. Further optimization focusing on maximizing in vivo efficacy and minimizing CYP3A4 time-dependent inhibition resulted in a highly efficacious compound (6s) in tumor xenograft model for further preclinical development.
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Organic Chemistry
Authors
Gang Liu, Sunny Abraham, Xing Liu, Shimin Xu, Allison M. Rooks, Ron Nepomuceno, Alan Dao, Daniel Brigham, Dana Gitnick, Darren E. Insko, Michael F. Gardner, Patrick P. Zarrinkar, Ron Christopher, Barbara Belli, Robert C. Armstrong, Mark W. Holladay,