WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 408159
CAS#: 2499663-01-1
Description: STM2457 is a highly potent and selective first-in-class catalytic inhibitor of METTL3. Treatment of tumours with STM2457 leads to reduced AML growth and an increase in differentiation and apoptosis. These cellular effects are accompanied by selective reduction of m6A levels on known leukaemogenic mRNAs and a decrease in their expression consistent with a translational defect. Pharmacological inhibition of METTL3 in vivo leads to impaired engraftment and prolonged survival in various mouse models of AML, specifically targeting key stem cell subpopulations of AML.
MedKoo Cat#: 408159
Name: STM2457
CAS#: 2499663-01-1
Chemical Formula: C25H28N6O2
Exact Mass: 444.2274
Molecular Weight: 444.539
Elemental Analysis: C, 67.55; H, 6.35; N, 18.91; O, 7.20
Synonym: STM2457; STM-2457; STM 2457;
IUPAC/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
InChi Key: OBERVORNENYOLE-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H28N6O2/c32-24-12-21(29-23-8-4-5-11-31(23)24)25(33)27-15-20-17-30-16-19(9-10-22(30)28-20)14-26-13-18-6-2-1-3-7-18/h4-5,8-12,16-18,26H,1-3,6-7,13-15H2,(H,27,33)
SMILES Code: C1=CC=CC2=NC(C(=O)NCC3N=C4C=CC(CNCC5CCCCC5)=CN4C=3)=CC(=O)N12
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | STM2457 is a highly potent and selective first-in-class catalytic inhibitor of RNA Methyltransferase METTL3 with an IC50 of 16.9 nM. STM2457 is highly specific for METTL3 and showed no inhibition of other RNA methyltransferases. |
| In vitro activity: | TBD |
| In vivo activity: | Treatment of tumours with STM2457 leads to reduced AML growth and an increase in differentiation and apoptosis. These cellular effects are accompanied by selective reduction of m6A levels on known leukaemogenic mRNAs and a decrease in their expression consistent with a translational defect. We demonstrate that pharmacological inhibition of METTL3 in vivo leads to impaired engraftment and prolonged survival in various mouse models of AML, specifically targeting key stem cell subpopulations of AML. Collectively, these results reveal the inhibition of METTL3 as a potential therapeutic strategy against AML, and provide proof of concept that the targeting of RNA-modifying enzymes represents a promising avenue for anticancer therapy. Reference: Yankova E, Blackaby W, Albertella M, Rak J, De Braekeleer E, Tsagkogeorga G, Pilka ES, Aspris D, Leggate D, Hendrick AG, Webster NA, Andrews B, Fosbeary R, Guest P, Irigoyen N, Eleftheriou M, Gozdecka M, Dias JML, Bannister AJ, Vick B, Jeremias I, Vassiliou GS, Rausch O, Tzelepis K, Kouzarides T. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021 May;593(7860):597-601. doi: 10.1038/s41586-021-03536-w. Epub 2021 Apr 26. PMID: 33902106. |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 89.0 | 200.21 | |
| Ethanol | 89.0 | 200.21 |
The following data is based on the product molecular weight 444.539 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | Yankova E, Blackaby W, Albertella M, Rak J, De Braekeleer E, Tsagkogeorga G, Pilka ES, Aspris D, Leggate D, Hendrick AG, Webster NA, Andrews B, Fosbeary R, Guest P, Irigoyen N, Eleftheriou M, Gozdecka M, Dias JML, Bannister AJ, Vick B, Jeremias I, Vassiliou GS, Rausch O, Tzelepis K, Kouzarides T. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021 May;593(7860):597-601. doi: 10.1038/s41586-021-03536-w. Epub 2021 Apr 26. PMID: 33902106. |
| In vitro protocol: | TBD |
| In vivo protocol: | Yankova E, Blackaby W, Albertella M, Rak J, De Braekeleer E, Tsagkogeorga G, Pilka ES, Aspris D, Leggate D, Hendrick AG, Webster NA, Andrews B, Fosbeary R, Guest P, Irigoyen N, Eleftheriou M, Gozdecka M, Dias JML, Bannister AJ, Vick B, Jeremias I, Vassiliou GS, Rausch O, Tzelepis K, Kouzarides T. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021 May;593(7860):597-601. doi: 10.1038/s41586-021-03536-w. Epub 2021 Apr 26. PMID: 33902106. |
Yankova E, Blackaby W, Albertella M, Rak J, De Braekeleer E, Tsagkogeorga G, Pilka ES, Aspris D, Leggate D, Hendrick AG, Webster NA, Andrews B, Fosbeary R, Guest P, Irigoyen N, Eleftheriou M, Gozdecka M, Dias JML, Bannister AJ, Vick B, Jeremias I, Vassiliou GS, Rausch O, Tzelepis K, Kouzarides T. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021 May;593(7860):597-601. doi: 10.1038/s41586-021-03536-w. Epub 2021 Apr 26. PMID: 33902106.
N6-methyladenosine (m6A) is an abundant internal RNA modification that is catalysed predominantly by the METTL3-METTL14 methyltransferase complex. The m6A methyltransferase METTL3 has been linked to the initiation and maintenance of acute myeloid leukaemia (AML), but the potential of therapeutic applications targeting this enzyme remains unknown.
