KDOAM-25 trihydrochloride increases global H3K4 methylation at transcriptional start sites and impairs proliferation in multiple myeloma MM1S cells. KDOAM-25 trihydrochloride is a potent and highly selective histone lysine demethylases 5 (KDM5) inhibitor with IC50s of 71 nM, 19 nM, 69 nM, 69 nM for KDM5A, KDM5B, KDM5C, KDM5D, respectively.

KDM5D:69 nM , KDM5A:71 nM , KDM5B:19 nM , KDM5C:69 nM

KDOAM-25 trihydrochloride is able to reduce the viability of MM1S cells with an IC50 of ～30 μM after a delay of 5-7 days. KDOAM-25 trihydrochloride treatment results in a G1 cell-cycle arrest with an increased proportion of MM1S in G1 and a decrease of the proportion of cells in G2 without an increase in the proportion of cells in the apoptotic sub-G1 phase. KDOAM-25 trihydrochloride (50 μM) increases with approximately twice as much H3K4me3 in in multiple myeloma cells. KDOAM-25 trihydrochloride inhibits most potently KDM5B with an IC50 of ～50 μM and the other KDM5 family members at concentrations above 100 μM. KDOAM-25 trihydrochloride shows no cellular activity on any of the other tested JmjC family members.