STM2457 是一流的、高效、选择性和口服活性的 METTL3 抑制剂，IC50 为 16.9 nM。 STM2457可用于急性髓性白血病（AML）的研究。
货号:ajcx12022
CAS:2499663-01-1
分子式:C25H28N6O2
分子量：444.53
溶解度:DMSO : 270 mg/mL
纯度：98%
存储：Store at -20°C
库存：现货

Background:

STM2457, an inhibitor of METTL3-METTL14 catalytic activity with IC₅₀of 16.9 nM, can directly bind to the METTL3-METTL14 with a high affinity (K_d) 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 expansionin vivoand significantly prolong the mouse lifespan. It also reduces human CD45⁺cells in the bone marrow and spleen.^[1]

参考文献:
[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).

Protocol:

Kinase experiment [1]:
Inhibition of METTL3-METTL14	STM2457 inhibits METTL3-METTL14 activity with IC50 of 16.9 nM.
Cell experiment [1]:
Cell lines	Human AML cells, mouse AML cells, MOLM-13
Preparation method	The solubility of this compound in DMSO is > 1 mM.
Reaction Conditions	3 days
Applications	STM2457 shows its anti-leukaemic activity by the pharmacological inhibition of METTL3 on SP1 and BRD4.
Animal experiment [1]:
Animal models	NSG mice (primary murine MLL-AF9/Flt3ITD/+)
Dosage form	50 mg/kg, intraperitoneal injection, STM2457 was dissolved in 20% (w/v) 2-hydroxyprolpy β-cyclodextrin vehicle.
Applications	STM2457 decrease total m6A levels on poly-A+-enriched RNA of METTL3, reduces human CD45+cells in the bone marrow and spleen and impair engraftment and AML expansion in vivo at the dose of 50 mg/kg.
参考文献: [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).