WM-8014 (WM8014) is a highly potent, selective inhibitor of lysine acetyltransferase KAT6A with Kd of 5 nM and IC50 of 8 nM.
WM-8014 is reversible competitor of acetyl coenzyme A and inhibits MYST-catalysed histone acetylation, also inhibits closely related KAT6B (IC50=28 nM), displays >10-fold selectivity over KAT7 and KAT5 (IC50=342 nM and 224 nM), shows no inhibition against KAT8, KAT2A, KAT2B, KAT3A and KAT3B.
WM-8014 induces cell cycle exit and cellular senescence without causing DNA damage, reduces acetylation of specific histone lysine residues and changes in gene expression that resemble the genetic loss of KAT6A.
WM-8014 selectively reduces liver volume in a zebrafish model of KRASG12V-driven hepatocellular overproliferation, robustly upregulate the cell cycle regulators Cdkn2a and Cdkn1a in hepatocytes.
