WM-3835 is a potent and high-specific HBO1 (KAT7 or MYST2) inhibitor and binds directly to the acetyl-CoA binding site of HBO1 33. WM-3835 activates apoptosis while inhibits osteosarcoma (OS) cell proliferation, migration and invasion. WM-3835 has antitumor activity and potently inhibits pOS-1 xenograft growth in mice[1].
WM-3835 (1-25 uM; 24-96 hours) inhibits pOS-1 cell viability in a concentration-dependent manner[1]. WM-3835 (5 uM; 72 h) activates cell apoptosis and significantly increases TUNEL-positive nuclei in pOS-1 cells[1]. WM-3835 (5 µM; 24 hours) downregulates MYLK-HOXA9 mRNA expression in pOS-1 cells[1]. WM-3835 (1-25 uM) suppresses H4K12ac-H3K14ac in a dose-dependent manner. WM-3835 does not alter the expressions of HBO1 protein and total H3, H4 histones[1]. WM-3835 (5 µM) fails to induce apoptosis and reduction of viability in HBO1-KO pOS-1 cells, koHBO1-1 and koHBO1-2, HBO1-low human osteoblasts[1].
WM-3835 (10 mg/kg/day; ip; for21 days) potently inhibits pOS-1 xenograft growth in SCID mice[1].
[1]. Yan-Yang Gao, et al. The histone acetyltransferase HBO1 functions as a novel oncogenic gene in osteosarcoma. Theranostics. 2021 Mar 4;11(10):4599-4615.