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]