MM-102 is a small molecule WDR5/MLL1 protein-protein interaction inhibitor. MM-102 in bone marrow cells transduced with MLL1-AF9 fusion construct decreases the expression of HoxA9 and Meis-1, two critical MLL1 target genes in MLL1 fusion protein mediated leukemogenesis.
mm-102 is an antagonist of mll1 with ic50 value of 2.4nm [1].mixed lineage leukemia 1 (mll1) is a histone h3 lysine 4 (h3k4) methyltransferase. the interaction of mll1 and wdr5 is essential for mll1 enzymatic activity and is a target for the treatment of acute leukemia. mm-102 is a peptidomimetic of mll1. it has a high binding affinity to wdr5 with ic50 value of 2.4nm [1].mm-102 is reported to reduce the expression of mll1 targeted genes hoxa9 and meis-1 in mll1-af9 transduced murine cells. since these two genes are required for mll1 mediated leukemogenesis, mm-102 is found to inhibit cell growth of leukemia cells harboring mll1 fusion proteins. it dose-dependently inhibits the cell growth in the mv4;11 and kopn8 cell lines with ic50 values both of 25μm[1].
[1] karatas h, townsend ec, cao f, chen y, bernard d, liu l, lei m, dou y, wang s. high-affinity, small-molecule peptidomimetic inhibitors of mll1/wdr5 protein-protein interaction. j am chem soc. 2013 jan 16;135(2):669-82.
