@article{32782823eae949678c167069365de90d,
title = "Discovery of benzoylsulfonohydrazides as potent inhibitors of the histone acetyltransferase KAT6A",
abstract = "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 μM. 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 μM). 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.",
author = "Leaver, {David J.} and Benjamin Cleary and Nghi Nguyen and Daniel Priebbenow and Lagiakos, {H. Rachel} and Julie Sanchez and Lian Xue and Fei Huang and Yuxin Sun and Prashant Mujumdar and Ramesh Mudududdla and Swapna Varghese and Silvia Teguh and Charman, {Susan A.} and White, {Karen L.} and Kasiram Katneni and Matthew Cuellar and Strasser, {Jessica M.} and Dahlin, {Jayme L.} and Walters, {Michael A.} and Street, {Ian P.} and Monahan, {Brendon J.} and Jarman, {Kate E.} and Sabroux, {Helene Jousset} and Hendrik Falk and Chung, {Matthew C.} and Hermans, {Stefan J.} and Parker, {Michael W.} and Tim Thomas and Baell, {Jonathan B.}",
year = "2019",
month = aug,
day = "8",
doi = "10.1021/acs.jmedchem.9b00665",
language = "English",
volume = "62",
pages = "7146--7159",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "15",
}