STM-005

STM-005 is a potent and selective small molecule inhibitor of the RNA methyltransferase METTL3 (Methyltransferase-like 3), developed by Storm Therapeutics. METTL3 is the catalytic subunit of the m6A methyltransferase complex, which installs N6-methyladenosine (m6A) modifications on mRNA—a critical regulatory mechanism in epitranscriptomics. In various cancers, particularly acute myeloid leukemia (AML), METTL3 is frequently overexpressed, leading to the aberrant methylation and increased translation of oncogenic transcripts that drive leukemogenesis and inhibit cellular differentiation. STM-005 functions by binding to the S-adenosylmethionine (SAM) binding site of METTL3, thereby inhibiting its enzymatic activity. This inhibition results in a global reduction of m6A levels, specifically downregulating the expression of key oncogenic drivers such as SP1, BCL2, and MYC, which induces growth arrest and apoptosis in cancer cells. While Storm Therapeutics has advanced other candidates like STC-15 into clinical trials, STM-005 remains a significant preclinical asset and tool compound in the study of METTL3-mediated RNA modification.