STM9005 is a potent, highly specific inhibitor of m7G methyltransferase METTL1, inhibits recombinant METTL1 enzyme activity with an IC50 < 13 nM and SPR Kd of 2 nM, affects METTL1-mediated m7G modification in cancer cells.
STM9005 shows cell penetration and binding to METTL1 in cells with an IC50 of 13 nM in cellular target engagement assays.
STM9005 has no effect on the activity of other RNA-methyltransferases (METTL3/14, METTL16, BCDIN3D, TSG1 and NSUN2).
STM9005 also displays >10,000-fold selectivity for METTL1-WDR4 when tested against a broad panel of 49 RNA-, DNA- and protein-methyltransferases.
STM9005 potently decreases tRNA-Val-m7G in antibody-based m7G detection assays with IC50 of 34 nM.
STM9005 binds to the SAM-binding site of METTL1.
STM9005 causes cellular changes and cell cycle dysregulation in various cancer models (eg. HL-60 cell IC50=7.5 uM).
STM9005 reduces m7G on tRNAs and impacts METTL1 catalytic-dependent mRNA translation.
STM9005 shows anti-tumour activity in a range of cancer models.