| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1368716 | Bioorganic & Medicinal Chemistry Letters | 2016 | 5 Pages |
Abstract
Structure based design of a novel class of aminopyrimidine MTH1 (MutT homolog 1) inhibitors is described. Optimization led to identification of IACS-4759 (compound 5), a sub-nanomolar inhibitor of MTH1 with excellent cell permeability and good metabolic stability in microsomes. This compound robustly inhibited MTH1 activity in cells and proved to be an excellent tool for interrogation of the utility of MTH1 inhibition in the context of oncology.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Alessia Petrocchi, Elisabetta Leo, Naphtali J. Reyna, Matthew M. Hamilton, Xi Shi, Connor A. Parker, Faika Mseeh, Jennifer P. Bardenhagen, Paul Leonard, Jason B. Cross, Sha Huang, Yongying Jiang, Mario Cardozo, Giulio Draetta, Joseph R. Marszalek,