Journal
CHEMMEDCHEM
Volume 12, Issue 21, Pages 1776-1793Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201700447
Keywords
antitumor agents; CDK; drug design; PTEFb; sulfoximines
Categories
Funding
- Max Planck Foundation on behalf of the Max Planck Society
- Ministry for Research and Technology (BMBF) [0315326]
Ask authors/readers for more resources
Selective inhibition of exclusively transcription-regulating PTEFb/CDK9 is a promising new approach in cancer therapy. Starting from lead compound BAY-958, lead optimization efforts strictly focusing on kinase selectivity, physicochemical and DMPK properties finally led to the identification of the orally available clinical candidate atuveciclib (BAY 1143572). Structurally characterized by an unusual benzyl sulfoximine group, BAY 1143572 exhibited the best overall profile in vitro and in vivo, including high efficacy and good tolerability in xenograft models in mice and rats. BAY 1143572 is the first potent and highly selective PTEFb/CDK9 inhibitor to enter clinical trials for the treatment of cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available