EM127

EM127 (compound 11c) is a SMYD3 covalent inhibitor with high selectivity, high affinity (KD=13 μM) and site-specificity. EM127 effectively inhibits ERK1/2 phosphorylation and reduces transcriptional regulation of SMYD3 target genes. EM127 effectively and prolongedly impairs methyltransferase activity. EM127 can be used in cancer research, particularly in SMYD3 positive tumours[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

SMYD3

EM127 (5 μM; 24, 48, 72 h) shows good anti-proliferative activity in MDA-MB-231and HCT116 cells[1]. EM127 (5 μM; 24, 48, 72 h) attenuates the expression of SMYD3 target genes while does not affect expression when SMYD3 is knocked out or expressed at low levels in MDA-MB-231 cells[1]. EM127 (1, 3.5, 5 μM; 48, 72 h) decreases ERK1/2 phosphorylation in a dose- and time-dependent manner in HCT116 and MDA-MB-231cells[1]. Cell Proliferation Assay[1] Cell Line: MDA-MB-231, HCT116 cells Concentration: 5 μM Incubation Time: 24, 48, 72 h Result: Significantly retarded cell proliferation by 48 h. RT-PCR[1] Cell Line: MDA-MB-231 cells Concentration: 0.5, 3.5, 5 μM Incubation Time: 48 h Result: Significantly reduced the expression of CDK2 and C-MET, the known SMYD3 regulated genes. Attenuated the abundance of mRNAs of the extracellular matrix component fibronectin 1 (FN1) and N-cadherin (N-CAD). Western Blot Analysis[1] Cell Line: HCT116, MDA-MB-231cells Concentration: 1, 3.5, 5 μM Incubation Time: 48, 72 h Result: Attenuated ERK1/2 phosphorylation and induced PARP processing at the same concentrations that retarded cell proliferation.

[1]. Parenti M D, et al. Discovery of the 4-aminopiperidine-based compound EM127 for the site-specific covalent inhibition of SMYD3. European Journal of Medicinal Chemistry, 2022: 114683.