STM2457 is a first-in-class, highly potent, selective and orally active inhibitor of METTL3 . It can be used for the research of acute myeloid leukaemia (AML).

STM2457 (Compound 72) inhibits MOLM13 cells proliferation with an IC50?of 8.699 μM[1]. STM2457, a highly potent and selective first-in-class catalytic inhibitor of METTL3, and a crystal structure of STM2457 in complex with METTL3-METTL14. 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[2].

2499663-01-1

C25H28N6O2

444.539

STM2457

[1]Eliza Yankova, et al. Small molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021 Apr 26. [2]Wesley Peter Blackaby, et al. Mettl3 inhibitory compounds. WO2020201773A1.

[1]Xu Q C, Tien Y C, Shi Y H, et al. METTL3 promotes intrahepatic cholangiocarcinoma progression by regulating IFIT2 expression in an m6A-YTHDF2-dependent manner. Oncogene. 2022: 1-12. [2]Zhao T, Zhao R, Yi X, et al. METTL3 promotes proliferation and myogenic differentiation through m6A RNA methylation/YTHDF1/2 signaling axis in myoblasts. Life Sciences. 2022: 120496.

DMSO:125 mg/mL (281.20 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years