SS-208 is an inhibitor of histone deacetylase 6 (HDAC6; IC50 = 12 nM).1 It is selective for HDAC6 over HDAC1, -4, -5, -7, -8, -9, and -11 (IC50s = 1.39, 19.5, 6.91, 8.34, 1.23, 38.2, and 5.12 μM, respectively). SS-208 (0.1-25 μM) inhibits HDAC6 in, but does not induce cell death of, human PC3 prostate, 5637 and T24 bladder, and murine SM1 melanoma cells in vitro. It decreases protein levels of programmed death ligand 1 (PD-L1) in SM1 cells when used at a concentration of 5 μM. SS-208 (25 mg/kg, i.p.) reduces tumor growth and increases the number of intratumoral CD8+, CD4+, and natural killer (NK) T cells in an SM1 murine melanoma model.
|1. Shen, S., Hadley, M., Ustinova, K., et al. Discovery of a new isoxazole-3-hydroxamate-based histone deacetylase 6 inhibitor SS-208 with antitumor activity in syngeneic melanoma mouse models. J. Med. Chem. 62(18), 8557-8577 (2019).