SMIR-181

SMIR-181 is a first-in-class small molecule inhibitor designed to target the biogenesis of oncogenic microRNA-181a (miR-181a). miR-181a is a master regulator of tumor pathogenesis, influencing cancer initiation, progression, and immune evasion by suppressing critical pathways such as STING, WNT, and TGFβ signaling. SMIR-181 acts by inducing the degradation of TARBP2 (Trans-Activating Responsive Binding Protein 2), an RNA-binding protein that serves as a rheostat for stress-induced miRNAs. This degradation leads to the accumulation of precursor miR-181a and a corresponding depletion of the mature, oncogenic form. Developed by researchers at the University of Michigan and collaborating institutions, SMIR-181 has demonstrated broad cytotoxicity across the NCI-60 cancer cell line panel, showing enhanced efficacy in miR-181a-high tumor cells while sparing normal cells. It represents a novel pharmacological strategy to overcome the bioavailability and stability challenges associated with nucleotide-based miRNA therapies.

Other names

Small Molecule Inhibitor of miR-181a