APHA compound 8 is an inhibitor of class I histone deacetylases (HDACs; IC50s = 3.7, 7.4, 0.42, and 2.8 μM for HDAC1, -2, -3, and -8, respectively) as well as class II HDACs (IC50s = 3.1, 0.1, 3.1, and 4.2 μM for HDAC4, -6, -7, and -10, respectively). It is selective for class I and II HDACs over class III HDACs (IC50s = >30 μM for SIRT1, SIRT2, and SIRT3) and the histone acetyltransferase PCAF (IC50 = >30 μM). At 48 hours post-infection, APHA compound 8 increases replication of oncolytic herpes simplex virus (oHSV) in MDA-MB-231 and 4T1 breast cancer cells when used prior to viral infection at concentrations of 10 and 50 μM.
