STM2457 |
Catalog No.GC19771
One-Click Copy Product Info
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A first-in-class, highly potent, selective and orally active METTL3 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
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]
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 | |
| Chemical Name | 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 | ||
| Formula | C25H28N6O2 | M.Wt | 444.53 |
| Solubility | DMSO : 270 mg/mL | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2496 mL | 11.2478 mL | 22.4957 mL |
| 5 mM | 449.9 μL | 2.2496 mL | 4.4991 mL |
| 10 mM | 225 μL | 1.1248 mL | 2.2496 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- 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
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