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Identification of potent and selective MTH1 inhibitors.
Petrocchi, Alessia; Leo, Elisabetta; Reyna, Naphtali J; Hamilton, Matthew M; Shi, Xi; Parker, Connor A; Mseeh, Faika; Bardenhagen, Jennifer P; Leonard, Paul; Cross, Jason B; Huang, Sha; Jiang, Yongying; Cardozo, Mario; Draetta, Giulio; Marszalek, Joseph R; Toniatti, Carlo; Jones, Philip; Lewis, Richard T.
Affiliation
  • Petrocchi A; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA. Electronic address: apetrocchi@mdanderson.org.
  • Leo E; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Reyna NJ; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Hamilton MM; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Shi X; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Parker CA; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Mseeh F; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Bardenhagen JP; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Leonard P; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Cross JB; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Huang S; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Jiang Y; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Cardozo M; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Draetta G; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Marszalek JR; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Toniatti C; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Jones P; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
  • Lewis RT; Institute for Applied Cancer Science, MD Anderson Cancer Center, 1901 East Road, Houston (TX) 77054, USA.
Bioorg Med Chem Lett ; 26(6): 1503-1507, 2016 Mar 15.
Article in En | MEDLINE | ID: mdl-26898335
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phosphoric Monoester Hydrolases / DNA Repair Enzymes / Enzyme Inhibitors Type of study: Diagnostic_studies Limits: Humans Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2016 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phosphoric Monoester Hydrolases / DNA Repair Enzymes / Enzyme Inhibitors Type of study: Diagnostic_studies Limits: Humans Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2016 Document type: Article