MM-102

MM-102 (HMTase Inhibitor IX) is a cell-permeable and tightly binding inhibitor of MLL1-WDR5 interaction (IC₅₀=2.4 nM). MM-102 can specifically inhibit the growth and induce apoptosis of leukemia cells containing MLL1 fusion protein, and reduce renal fibrosis and inflammation in mice with ischemia-reperfusion injury. In addition, MM-102 also acts as an H3K4 histone methyltransferase inhibitor to improve the development of porcine somatic cell nuclear transfer (SCNT) embryos^{[1][2][3][4][5]}. In Vitro:MM-102 (40 µM; 4 d) induces growth arrest and cell death in MLL1-AF9-transformed mouse leukemia cells specifically in leukemia cells harboring the MLL1 translocation, but does not interfere with the growth of normal bone marrow^[2].
MM-102 (2, 10, and 50 µM) disrupts the association of WDR5 and RbBP5 with GSTMLL1 in a concentration-dependent manner. The association of WDR5 with MLL1 is mildly disrupted at 2 µM, moderately disrupts at 10 µM, and completely disrupts at 50 µM^[2].
MM-102 specifically inhibits the methyltransferase activity of the MLL1 complex with an IC₅₀ value of 0.32 µM^[2].
MM-102 (50 µM; 48 h) can significantly inhibit the proliferation, migration and chemoresistance of TFK1 and RBE cells^[3].
MM-102 (50 µM; 1 h) not only significantly reduces the expression of MLL1, WDR5 and H3K4me3 in TGF-b1-stimulated NRK-49F cells, but also inhibits the expression of p16INK4a^[4].
MM-102 (50-100 μM; 48 h) enhances the developmental competence of porcine SCNT embryos and improves the expression pattern of key genes in SCNT embryo development^[5].
In Vivo:MM-102 (15 mg/kg; i.p.; once daily for 7 days) inhibits tumor progression in primary CCA model mice^[3].
MM-102 (15 mg/kg; i.p.; once daily for 7 days) inhibits p16INK4a gene expression in IRI mice and reduces renal fibrosis and renal inflammation in IRI mice^[4].