tcsc0965 Ricolinostat

Ricolinostat (ACY-1215) is a potent and selective HDAC6 inhibitor, with an IC₅₀ of 5 nM. ACY-1215 also inhibits HDAC1, HDAC2, and HDAC3 with IC₅₀s of 58, 48, and 51 nM, respectively.

IC50 & Target: IC50: 5 nM (HDAC6), 58 nM (HDAC1), 48 nM (HDAC2), 51 nM (HDAC3)^[1]

In Vitro: Ricolinostat (ACY-1215) has slight activity against HDAC8 (IC₅₀=0.1 μM), and has minimal activity (IC₅₀>1 μM) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2. The effect of Ricolinostat (ACY-1215) on multiple myeloma (MM) cell viability is determined with MTT assays using MM cell lines. Exposure of MM cell lines for 48 hours results in dose-dependent decreased viability, with IC₅₀ values ranging from 2-8μM. Ricolinostat (ACY-1215) demonstrates significant activity in the MM Bortezomib-resistant cell line (ANBL-6.BR), demonstrating the ability of Ricolinostat (ACY-1215) to overcome Bortezomib resistance^[1].

In Vivo: Mice treated with Ricolinostat (ACY-1215), Bortezomib, or Ricolinostat plus Bortezomib show a significant delay in tumor growth (P=0.01, P=0.006, and P<0.0001, respectively). Combined treatment with Ricolinostat and Bortezomib shows significant suppression of tumor growth and significantly prolonged overall survival (OS) compare with the control group (17 days in the control vs 40 days in the combination-treated group, P<0.0001) and the Ricolinostat (ACY-1215)-treated group (22 days in the Bortezomib group vs 40 days in the combination-treated group, P<0.0001). Weight loss in the combination-treated group is between 4% and 12% compare with the same-day control group values during treatment, with complete recovery after the last injection. As is observed in the plasmacytoma model, a significant therapeutic advantage is found by combining Ricolinostat with Bortezomib compare with either agent alone^[1].