2. Academic Validation
  3. Identification of potent and selective MTH1 inhibitors

Identification of potent and selective MTH1 inhibitors

  • Bioorg Med Chem Lett. 2016 Mar 15;26(6):1503-1507. doi: 10.1016/j.bmcl.2016.02.026.
Alessia Petrocchi 1,  Elisabetta Leo 2,  Naphtali J Reyna 2,  Matthew M Hamilton 2,  Xi Shi 2,  Connor A Parker 2,  Faika Mseeh 2,  Jennifer P Bardenhagen 2,  Paul Leonard 2,  Jason B Cross 2,  Sha Huang 2,  Yongying Jiang 2,  Mario Cardozo 2,  Giulio Draetta 2,  Joseph R Marszalek 2,  Carlo Toniatti 2,  Philip Jones 2,  Richard T Lewis 2
Affiliations

Affiliations

  • 1 Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA. Electronic address: apetrocchi@mdanderson.org.
  • 2 Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
PMID: 26898335 DOI: 10.1016/j.bmcl.2016.02.026
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.

Keywords

2-Aminopyrimidine; Antitumor; IACS-4759; MTH1 inhibitors.

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