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
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
More Info
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.
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 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 |
mg/mL |
mM |
| Solubility |
| DMSO |
89.0 |
200.21 |
| Ethanol |
89.0 |
200.21 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
444.54
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 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.
