Rocilinostat

Rocilinostat (also known as ACY 1215) is a selective HDAC6 inhibitor with potential antineoplastic activity. Rocilinostat (ACY-1215) selectively targets and binds to HDAC6, thereby disrupting the Hsp90 protein chaperone system through hyperacetylation of Hsp90 and preventing the subsequent aggresomal protein degradation. ACY-1215 has minimal activity (IC50 >1 μM) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1 and Sirtuin2, and has slight activity against HDAC8 (IC50 = 0.1 μM). In vivo, the anti-MM activity of rocilinostat in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously and luciferase-expressing human MM injected intravenously. Rocilinostat (ACY-1215) induces potent acetylation of α-tubulin at very low doses and triggers acetylation of lysine on histone H3 and histone H4 only at higher doses. Compared to non-selective HDAC inhibitor, ACY-1215 is able to reduce the toxic effects on normal, healthy cells.