We have located links that may give you full text access.
Discovery of a novel chemotype of histone lysine methyltransferase EHMT1/2 (GLP/G9a) inhibitors: rational design, synthesis, biological evaluation and co-crystal structure.
Journal of Medicinal Chemistry 2019 Februrary 13
Since the discovery of compound BIX01294 over 10 years ago, only a very limited number of non-quinazoline inhibitors of H3K9-specific methyltransferases G9a and GLP have been reported. Herein we report the identification of a novel chemotype for G9a/GLP inhibitors, based on the under-investigated 2-alkyl-5-amino- and 2-aryl-5-amino-substituted 3H-benzo[e][1,4]diazepine scaffold. Our research efforts yielded the identification of compound 12a (EML741), which not only maintained the high in vitro and cellular potency of its quinazoline counterpart, but also displayed improved inhibitory potency against DNMT1, improved selectivity against other methyltransferases, low cell toxicity, and improved apparent permeability values in both PAMPA and PAMPA-BBB assays and, therefore, might potentially be a better candidate for animal studies. Finally, the co-crystal structure of GLP in complex with 12a provides the basis for the further development of benzodiazepine-based G9a/GLP inhibitors.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app