SID 3712249 inhibits the biogenesis of microRNA-544 (miR-544), a silencer of mammalian target of rapamycin (mTOR).1 Under hypoxic conditions, SID 3712249 (20 nM) increases MTOR mRNA expression and decreases the mRNA expression of the genes encoding miR-544, hypoxia-inducible factor-1α (HIF-1α), and ataxia-telangiectasia mutated kinase (ATM) in MDA-MB-231, MCF-7, and MCF-10A cells. It induces apoptosis in MDA-MB-231 cells in a hypoxia- and mTOR-dependent manner when used at a concentration of 20 nM. SID 3712249 (20 nM) enhances the sensitivity of MCF-7 and MDA-MB-231 cells cultured under hypoxic conditions to decreases in cell viability induced by 5-fluorouracil . It reduces tumor growth in an MDA-MB-231 mouse xenograft model.
1.Haga, C.L., Velagapudi, S.P., Strivelli, J.R., et al.Small molecule inhibition of miR-544 biogenesis disrupts adaptive responses to hypoxia by modulating ATM-mTOR signalingACS Chem. Biol.10(10)2267-2276(2015)