Discovery of Benzoylsulfonohydrazides as potent inhibitors of the histone acetyltransferase KAT6A
Publication Year 2019-08-08,Volume 62,Issue #15,Page 7146-7159
Journal Title
Journal of Medicinal Chemistry
Publication Type
Journal Article
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 muM. 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 muM). 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.
WEHI Research Division(s)
Personalised Oncology; Advanced Technology And Biology; Epigenetics And Development
PubMed ID
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Creation Date: 2019-09-20 10:16:33
Last Modified: 2019-09-24 03:49:16
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