JQKD82 is a prodrug form of KDM5-C49, an inhibitor of Jumonji AT-rich interactive domain 1A (JARID1A), also known as lysine-specific demethylase 5A (KDM5A).1 It increases the levels of trimethylated lysine 4 on histone 3 (H3K4me3) in MOLP-8 and MM.1S multiple myeloma cells when used at concentrations of 0.3 and 1 ?M. JQKD82 reduces the proliferation of MOLP-8 and MM.1S cells in a concentration-dependent manner and decreases the viability of primary CD138+ cells from patients with multiple myeloma when used at a concentration of 3 ?M. It induces cell cycle arrest at the G0/G1 phase, as well as induces apoptosis, in MOLP-8 and MM.1S cells when used at a concentration of 1 ?M. JQKD82 (50 mg/kg twice per day) decreases tumor growth and increases survival in a MOLP-8 mouse xenograft model.
References:
[1]. Ohguchi, H., Park, P.M.C., Wang, T., et al.Lysine demethylase 5A is required for MYC-driven transcription in multiple myelomaBlood Cancer Discov.2(4)370-387(2021).