EM127 (C09-1130-747)

EM127 (compound 11c) is a SMYD3 covalent inhibitor with high selectivity, high affinity ( K D =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 tumoursIn VitroEM127 (5 μM; 24, 48, 72 h) shows good anti-proliferative activity in MDA-MB-231and HCT116 cells. 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. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: MDA-MB-231, HCT116 cells Concentration: 5 μM Incubation Time: 24, 48, 72 h Result: Significantly retarded cell proliferation by 48 h. RT-PCRCell 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 AnalysisCell 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.Form:SolidIC50& Target:SMYD3. Specification: 0.98 Molecular Formula: C14H18ClN3O3 Molecular Weight: 311.76