KDOAM-25, a potent and highly selective inhibitor of histone lysine demethylases 5 (KDM5) with IC50 values of 71 nM for KDM5A, 19 nM for KDM5B, 69 nM for KDM5C, and 69 nM for KDM5D, enhances global H3K4 methylation at transcriptional start sites and reduces proliferation in multiple myeloma MM1S cells.

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

KDOAM-25 treatment induces G1 cell-cycle arrest, characterized by an increased MM1S cell proportion in G1 phase and a decreased proportion in G2 phase, without affecting apoptotic sub-G1 phase cell counts. At a concentration of 50 μM, KDOAM-25 doubles the level of H3K4me3 in multiple myeloma cells, demonstrating strong inhibition of KDM5B at an IC50 of approximately 50 μM, while inhibiting other KDM5 family members at concentrations exceeding 100 μM. Furthermore, KDOAM-25 exhibits no activity against other JmjC family proteins and reduces MM1S cell viability with an IC50 of approximately 30 μM, manifesting effects after a 5-7 day period.