STM9005

STM9005 is a first-in-class, potent, and bioavailable small-molecule inhibitor of METTL1 (Methyltransferase-like 1), a tRNA methyltransferase that catalyzes the N7-methylation of guanine (m7G) in specific tRNAs. Developed by Storm Therapeutics, STM9005 targets the catalytic activity of METTL1, leading to decreased m7G methylation and lower levels of target tRNAs. This inhibition impairs cell proliferation and viability in aggressive malignancies such as acute myeloid leukemia (AML), melanoma, and pancreatic ductal adenocarcinoma (PDAC), while sparing non-cancerous cells. In preclinical models, STM9005 has demonstrated significant anti-cancer activity, including the induction of differentiation in AML and reduction of disease progression in patient-derived xenograft (PDX) models, with no detectable toxicity.