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 : GC19771
An inhibitor of the METTL3/14 complex
Cas No.:2499663-01-1
Sample solution is provided at 25 µL, 10mM.
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).
| 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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| 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 | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 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。
Quality Control & SDS
- View current batch:
- Purity: ≥99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Related Biological Data
The effects of m6A readers on AKT1 in three models of arsenic carcinogenesis. e AKT1 mRNA stability in three models after inhibiting METTL3 (using STM2457 or siMETTL3) or FTO (using FB23–2 or siFTO).
According to the previous studies (Huang et al., 2019; Yankova et al., 2021), three model cells were treated with vehicle (DMSO), 1 μM STM2457(GLPBIO), or 1 μM FB23–2 for 72 h and then harvested for further tests.
J Hazard Mater 445 (2023): 130468. PMID: 36444808 IF: 14.2235 -
Related Biological Data
STM2457 or FB23-2 was used to disturb the m6A levels in HaCaT cells exposed to 1 μM sodium arsenite for 0, 1, 4, 8, 22, and 22+12 w. Total m 6A levels were measured by EpiQuik m6A RNA methylation quantification kit.
Experimental cells were treated with 1 μM STM2457(GLPBIO), 1 μM FB23–2, or vehicle DMSO (Control group) for 72 h and harvested for detection.
J Hazard Mater (2023): 133329. PMID: 38142659 IF: 13.6006 -
Related Biological Data
Appendix Figure S7 Identification of m6A modifications on lncBMP4. B. The effects of STM2457 treatment on m6A enrichment levels in different regions of LncBMP4 in PGCs were detected by RIP-qPCR.
ESCs, PGCs, and DF-1 cells, transfected with Luc-LncBMP4 containing mutated RRACH sites, and PGCs treated with STM2457 (GLPBIO, GC19771) were collected. m6A enrichment on LncBMP4 was detected using the RIP assay, with an anti-m6A antibody.
EMBO reports (2021): e52491. PMID: 34747116 IF: 8.803