MM-589是WD重复结构域5(WDR5)和混合谱系白血病(MLL)相互作用的有效抑制剂。MM-589结合WDR5的IC50为0.90nM。抑制MLLH3K4甲基转移酶活性的IC50为12.7nM。
MM-589 is a potent inhibitor of WD repeat domain 5 (WDR5) and mixed lineage leukemia (MLL) interaction. MM-589 binds to WDR5 with an IC50 of 0.90 nM and inhibits the MLL H3K4 methyltransferase activity with an IC50 of 12.7 nM[1].
MM-589 binds to WDR5 with high affinity (IC50=0.90 nM, Ki <1 nM) and potently inhibits the MLL HMT activity (IC50=12.7 nM)[1].MM-589 (0.01-10 µM, 4 days or 7 days) potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations[1].|| Cell Viability Assay[1]||Cell Line:|MV4-11 and MOLM-13|Concentration:|0.1, 1, 10 μM|Incubation Time:|4 days or 7 days|Result:|MM-589 potently inhibits MV4-11 and MOLM-13 cell growth with IC50s of 0.25 and 0.21 μM, respectively. MM-589 has much weaker activity in the inhibition of cell growth of the HL-60 cell line with an IC50 of 8.6 μM[1].
MM-589 has excellent microsomal stability in human, mouse, and rat microsomes (T1/2 > 60 min). Further optimization of MM-589 may yield a new therapy for acute leukemia[1].
[1]. Karatas H, et al. Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)-Mixed Lineage Leukemia (MLL) Protein-Protein Interaction. J Med Chem. 2017 Jun 22;60(12):4818-4839.
动态评分
0.0