STM2457

• CAS: 2499663-01-1
• Catalog Number: ACM2499663011
• Category: Inhibitors
• Molecular Weight: 444.54
• Molecular Formula: C25H28N6O2
• 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.
• Synonyms: STM2457; STM-2457; STM 2457
• IUPAC 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: C1=CC=CC2=NC(C(=O)NCC3N=C4C=CC(CNCC5CCCCC5)=CN4C=3)=CC(=O)N12
• InChI: 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)
• InChI Key: OBERVORNENYOLE-UHFFFAOYSA-N
• Solubility: To be determined
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• 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.
• Drug Formulation: To be determined
• Elemental Analysis: C, 67.55; H, 6.35; N, 18.91; O, 7.20
• Exact Mass: 444.2274
• HS Tariff Code: 2934.99.9001
• 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.
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).