STM2457

An inhibitor of the METTL3/14 complex

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库存: 现货

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1mg

￥725.00

580.00

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5mg

￥2262.00

1810.00

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10mg

￥3787.00

3030.00

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50mg

￥10837.00

8670.00

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货号: ajcx12022
CAS: 2499663-01-1
别名: N-[[6-[[(环己基甲基)氨基]甲基]咪唑并[1,2-A]吡啶-2-基]甲基]-4-氧代-4H-吡啶并[1,2-A]嘧啶-2-甲酰胺
分子式: C25H28N6O2
分子量: 444.53
纯度: >98%
溶解度: DMSO : 270 mg/mL
储存: Store at -20°C
库存: 现货

Background

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 (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 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).

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/Flt3^ITD/+)
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).