Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 62, Issue 15, Pages 7146-7159Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.9b00665
Keywords
-
Categories
Funding
- National Health and Medical Research Council of Australia (NHMRC) [1030704, 1080146, 1020411, 1117602]
- Therapeutic Innovation Australia (TIA)
- Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program
- Victorian Government Operational Infrastructure Support Scheme
- National Health and Medical Research Council of Australia [1080146] Funding Source: NHMRC
Ask authors/readers for more resources
A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative (CTX-0124143) that inhibited KAT6A with an IC50 of 1.0 HM. Elaboration of the structure-activity relationship and medicinal chemistry optimization led to the discovery of WM-8014 (97), a highly potent inhibitor of KAT6A (IC50 = 0.008 /mu M). WM-8014 competes with acetyl-CoA (Ac-CoA), and X-ray crystallographic analysis demonstrated binding to the Ac-CoA binding site. Through inhibition of KAT6A activity, WM-8014 induces cellular senescence and represents a unique pharmacological tool,
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
Share Paper
