ML-60218

ML-60218 is a broad-spectrum RNA pol III inhibitor, with IC₅₀s of 32 and 27 μM 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^[1][2]. 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^[2].
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 μM ) viroplasm disruption causes NSP5 dephosphorylation^[3].