Butyroyloxymethyl-4-phenylbutyrate (AN-113) is a novel HDACI that releases potent anti-neoplastic derivatives upon intracellular hydrolysis. The precursor of AN-113, 4-phenylbutyrate has shown promising results in a Phase I study of gliomas, and we hypothesized that AN-113 offers significant advantages over the parent drug. AN-113 demonstrates selective in vitro cytotoxicity against malignant cells while sparing normal astrocytes, effective at doses over 20-fold lower than 4-phenylbutyrate. Combining AN-113 and radiation results in additive therapeutic effects. Enthusiasm is lent to this approach by the ability of AN-113 to efficiently kill glioma cells, its bioavailability and potency when administered orally, its capacity to cross the blood-brain barrier, and its effectiveness in combination with radiation.