MM-102 TFA

MM-102 (HMTase Inhibitor IX) TFA is a potent WDR5/MLL interaction inhibitor, achieves IC50 = 2.4 nM with an estimated Ki < 1 nM in WDR5 binding assay, which is >200 times more potent than the ARA peptide.

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

Research Areas >> Cancer

IC50: 2.4 nM (MLL)[1].

MM-102 (HMTase Inhibitor IX) inhibits MLL1 methyltransferase activity and MLL-1-induced HoxA9 and Meis-1 gene expression in leukemia cells expressing the MLL1-AF9 fusion gene. Also inhibits cell growth and induces apoptosis in leukemia cells harbouring MLL1 fusion proteins. MM-102 (TFA), with the highest binding affinities to WDR5, also show the most potent inhibitory activity in the HMT assay with IC50 = 0.4-0.9 μM. MM-102 (HMTase Inhibitor IX) dose-dependently inhibits cell growth in the MV4;11 and KOPN8 leukemia cell lines, which carry MLL1-AF4 and MLL1-ENL fusion proteins, respectively. MM-102 (HMTase Inhibitor IX) has IC50 = 25 μM in both cell lines and completely inhibits cell growth in these cell lines at 75 μM. MM-102 (HMTase Inhibitor IX) effectively and selectively inhibits cell growth and induces apoptosis in leukemia cells harboring MLL1 fusion proteins and has minimal effect in leukemia cells with wild-type MLL1 protein[1].

MV4;11, KOPN8, and K562 cells were cultured in RPMI 1640 medium (ATCC) supplemented with 10% fetal bovine serum and 100 U/L penicillinstreptomycin and incubated at 37°C under 5% CO2. Cells were seeded into 12-well plates for suspension at a density of 5 × 105 per well (1 mL) and treated with either vehicle control (DMSO, 0.2%) or MM-102 (HMTase Inhibitor IX) for 7 days. The medium was changed every 2 days, and compounds were resupplied. The CellTiter-Glo Luminescent Cell Viability Assay kit was used. First, 100 μL of the assay reagent was added into each well, and the content was mixed for 2 min on an orbital shaker to induce cell lysis. After 10 min incubation at room temperature, the luminescence was read on a microplate reader.

[1]. Karatas H, et al. High-affinity, small-molecule peptidomimetic inhibitors of MLL1/WDR5 protein-protein interaction. J Am Chem Soc. 2013 Jan 16;135(2):669-682.

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