ML-60218

577784-91-9

452.38

DMSO : 100 mg/mL (221.05 mM; Need ultrasonic)

Cell Cycle/DNA Damage

ML-60218 is a broad-spectrum RNA pol III inhibitor, with IC50s of 32 and 27 uM for Saccharomyces cerevisiae and human. ML-60218 disrupts already assembled viroplasms and to hamper the formation of new ones without the need for de novo transcription of cellular RNAs.
In Vitro: Combination of SAHA and ML-60218 produces enhanced suppression of proliferation in human pancreatic adenocarcinoma by impairing cell cycle progression and inducing apoptosis. ML-60218 reverses SAHA-stimulated tRNA expression in PANC-1 and BxPC-3 cells. ML-60218 enhances the ability of HDAC inhibitors to induce apoptosis and cell cycle arrest.

In in vitro transcription assays with purified double-layered particles (DLPs), ML-60218 shows dose-dependent inhibitory activity, indicating the viral nature of its target. ML-60218 is found to interfere with the formation of higher-order structures of VP6, the protein forming the DLP outer layer, without compromising its ability to trimerize. Electron microscopy of ML-60218-treated DLPs shows dose-dependent structural damage. ML-60218-mediated (10 uM ) viroplasm disruption causes NSP5 dephosphorylation.