WM-3835 (WM 3835) is a potent, high-specific, cell-permeable inhibitor of MYST acetyltransferase HBO1 (KAT7 or MYST2).
WM-3835 showed increased potency against HBO1 compared to WM-1119.
Treatment of a diverse set of AML cell lines with WM-3835 resulted in a marked reduction in tumour-cell viability, with an excellent dose-response relationship between a reduction of levels of H3K14ac,.
Treatment of cells with WM-3835 phenocopied the molecular and cellular effects of genetic depletion of HBO1 by inducing apoptosis, a G0/G1 cell-cycle arrest, differentiation of human AML cells and transcriptional repression on HOXA9 and HOXA10.
Inhibition of HBO1 phenocopied our genetic data and showed efficacy in a broad range of human cell lines and primary AML cells from patients.
