STM2457, an inhibitor of METTL3-METTL14 catalytic activity with IC50 of 16.9 nM, can directly bind to the METTL3-METTL14 with a high affinity (Kd) of 1.4 nM. STM2457, also shows greater than 1,000-fold selectivity for METTL3 compared to other RNA, DNA and protein methyltransferases. [1]
STM2457 can inhibit the proliferation of human AML cells but not normal non-lekaemic haemopoietic cells. What’s more, STM2457 can reduce the clonogenic potential of primary mouse AML cells and inhibit METTL3 in MOLM-13 cells, which causes myeloid differentiation and cell cycle arrest. [1]
STM2457 can impair engraftment and AML expansion in vivo and significantly prolong the mouse lifespan. It also reduces human CD45+cells in the bone marrow and spleen. [1]
STM2457是METTL3-METTL14催化活性的抑制剂，其IC50为16.9nM，可以以1.4nM的高亲和力（Kd）直接结合METTL3-METTL14。STM2457与其他RNA、DNA和蛋白质甲基转移酶相比，对METTL3也显示出大于1000倍的选择性。[1]
STM2457可以抑制人AML细胞的增殖，但不能抑制正常非白血病造血细胞的增殖。此外，STM2457可以降低原代小鼠AML细胞的克隆潜能，并抑制MOLM-13细胞中的METTL3，从而导致骨髓分化和细胞周期停滞。[1]
STM2457可在体内损害植入和AML扩增，并显著延长小鼠寿命。它还减少了骨髓和脾脏中的人类CD45+细胞。[1]
Reference:
[1] Yankova, E., Blackaby, W., Albertella, M. et al. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature 593, 597–601 (2021).