ML327

Description: ML327 is a novel potent MYC blocker which also de-represses E-cadherin transcription, partially reverses EMT (Epithelial-to-Mesenchymal Transition), and inhibits cancer cell invasiveness and tumor cell migration in vitro and in vivo. Induction of E-cadherin mRNA expression by ML327 treatment does not require de novo protein synthesis. RNA sequencing analysis revealed that ML327 treatment significantly alters expression of over 2, 500 genes within three hours in the presence of the translational inhibitor, cycloheximide. Network analysis reveals Hepatocyte Nuclear Factor 4-alpha (HNF4alpha) as the most significant upstream transcriptional regulator of multiple genes whose expressions were altered by ML327 treatment. Further, small interfering RNA-mediated depletion of HNF4alpha markedly attenuates the E-cadherin expression response to ML327. In summary, ML327 represents a valuable tool to understand mechanisms of EMT and may provide the basis for a novel targeted therapeutic strategy for carcinomas.

References: Oncotarget. 2015 Sep 8; 6(26):22934-48; Oncotarget. 2017 Jul 20; 8(53):91040-91051.