MM-401 TFA

MM-401 (TFA) is a MLL1 H3K4 methyltransferase inhibitor. MM-401 inhibits MLL1 activity (IC50 = 0.32 µM) by blocking MLL1-WDR5 interaction. MM-401 can induce cell cycle arrest, Apoptosis and differentiation. MM-401 can be used for the research of MLL leukemia[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

Ki: < 1 nM (WDR5); IC50: 0.9 nM (WDR5-MLL1 interaction), 0.32 µM (MLL1)[1].

MM-401 maintains high binding affinity to WDR5 with a Ki value of < 1 nM and disrupts WDR5-MLL1 interaction with an IC50 value of 0.9 nM[1]. MM-401 is able to specifically inhibit MLL1 activity (IC50 value of 0.32µM) by blocking MLL1-WDR5 interaction and thus the complex assembly[1]. MM-401 (20 μM; 48 h) specifically inhibits MLL1-dependent H3K4 methylation in cells[1]. MM-401 induces similar changes in MLL-AF9 transcriptome as the MLL1 deletion[1]. MM-401 (10, 20, 40 μM; 48 h) specifically inhibits growth of MLL leukemia cells by inducing cell cycle arrest, apoptosis[1]. Apoptosis Analysis[1] Cell Line: Murine MLL-AF9 and Hoxa9/Meis1 cells Concentration: 10, 20, 40 μM Incubation Time: 48 h Result: Specifically induced apoptosis of MLL-AF9 cells. Cell Cycle Analysis[1] Cell Line: Murine MLL-AF9 and Hoxa9/Meis1 cells Concentration: 10, 20, 40 μM Incubation Time: 48 h Result: Induced prominent G1/S arrest in MLL-AF9 cells in a concentration dependent manner. RT-PCR[1] Cell Line: MLL-AF9 cells Concentration: 20 μM Incubation Time: 48 h Result: Significantly decreased H3K4me, expression of 5 Hox A genes, especially Hoxa9 and Hoxa10.

[1]. Fang Cao, et al. Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Mol Cell. 2014 Jan 23;53(2):247-61.