STM2457
(Synonyms: 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) 目录号 : GC19771An inhibitor of the METTL3/14 complex
Sample solution is provided at 25 µL, 10mM.
| Kinase experiment [1]: | |
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Inhibition of METTL3-METTL14 |
STM2457 inhibits METTL3-METTL14 activity with IC50 of 16.9 nM. |
| Cell experiment [1]: | |
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Cell lines |
Human AML cells, mouse AML cells, MOLM-13 |
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Preparation method |
The solubility of this compound in DMSO is > 1 mM. |
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Reaction Conditions |
3 days |
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Applications |
STM2457 shows its anti-leukaemic activity by the pharmacological inhibition of METTL3 on SP1 and BRD4. |
| Animal experiment [1]: | |
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Animal models |
NSG mice (primary murine MLL-AF9/Flt3ITD/+) |
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Dosage form |
50 mg/kg, intraperitoneal injection, STM2457 was dissolved in 20% (w/v) 2-hydroxyprolpy β-cyclodextrin vehicle. |
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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. |
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References: [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). |
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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]
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).
| Cas No. | 2499663-01-1 | SDF | |
| 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 | ||
| 化学名 | N-((6-(((cyclohexylmethyl)amino)methyl)imidazo[1,2-a]pyridin-2-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carboxamide | ||
| Canonical SMILES | O=C(C(N=C1N2C=CC=C1)=CC2=O)NCC3=CN4C=C(CNCC5CCCCC5)C=CC4=N3 | ||
| 分子式 | C25H28N6O2 | 分子量 | 444.53 |
| 溶解度 | DMSO : 270 mg/mL | 储存条件 | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2496 mL | 11.2478 mL | 22.4957 mL |
| 5 mM | 0.4499 mL | 2.2496 mL | 4.4991 mL |
| 10 mM | 0.225 mL | 1.1248 mL | 2.2496 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。