MC4171 (KAT8 inhibitor 34) is a first-in-class, selective and reversible lysine acetyltransferase KAT8 inhibitor with IC50 of 8.1 uM and SPR Kd of 2.04 uM.
MC4171 displays high selectivity against a panel of KATs (KAT2A and the MYST family members KAT5, KAT6A, KAT6B, and KAT7), KDACs (KDAC1–3, 6, and 8).
MC4171 exhibits target engagement as stabilizing KAT8 against thermal-induced aggregation in cells.
MC4171 (50 uM) reduces more than 50% reduction of H4K16Ac in HT29 CRC cell line, with no influence on KAT8 expression levels or on H3K27 acetylation (acetylated by KAT3A/B).
MC4171 displayed antiproliferative activity in A549 cells (65% cell proliferation inhibition at 50 uM; 80% cell proliferation inhibition at 100 uM).
MC4171 is cancer-selective, exhibits mid-micromolar antiproliferative activity in different cancer cell lines, including NSCLC and AML, without impacting the viability of nontransformed cells.
MC4171 is valuable chemical tool for elucidating KAT8 biology.