Resminostat

Resminostat (4SC-201) is a novel, orally bioavailable histone deacetylase (HDAC) inhibitor for the treatment of cancers. Resminostat inhibited proliferation and induced G0/G1 cell cycle arrest in 3 out of 4 MM cell lines accompanied with decreased levels of cyclin D1, cdc25a, Cdk4 and pRb as well as upregulation of p21 at 1 micromol/l. Resminostat (4SC-201) induces hyperacetylation of histone H4 in MM cells. Low micromolar concentrations of resminostat (RAS2410) abrogated cell growth and strongly induced apoptosis (IC50=2.5-3 micromol/l in 3 out of 4 MM cell lines) in MM cell lines as well as primary MM cells. Resminostat decreased phosphorylation of 4E-BP1 and p70S6k indicating an interference with Akt pathway signalling. Resminostat treatment resulted in increased protein levels of Bim and Bax and decreased levels of Bcl-xL.