EM127 is a potent, site-specific covalent, second-generation inhibitor of SMYD3 methyltransferase.
EM127 shows a striking selectivity towards the target Cys186 residue.
EM127 is more potent than the reference inhibitor EPZ031686.
EM127 attenuated the proliferation of MDA-MB-231 breast cancer cell line at the same low micromolar range of concentrations that reduced SMYD3 mediated ERK signaling in HCT116 colorectal cancer and MDA-MB-231 breast cancer cells.
EM127 (5 μM) strongly decreased the steady-state mRNA levels of genes important for tumor biology such as cyclin dependent kinase 2, c-MET, N-cadherin and fibronectin 1, all known to be regulated, at least in part, by SMYD3.
