Epstein-Barr virus (EBV) is associated with a number of human lymphoid malignancies and carcinomas for which there are presently few effective treatments. Each year in the U.S., there are approximately 27,000 people afflicted with diseases caused by the Epstein-Barr virus, and an additional 107,000 people afflicted with malignancies associated with the Epstein-Barr virus. Worldwide, EBV-associated diseases are even more common, and current treatments are typically unsuccessful. Under FDA IND #47,529, we are currently testing Arginine Butyrate in combination with ganciclovir for treatment of these malignancies. Arginine Butyrate induces the latent EBV-enzyme thymidine kinase (TK), which, in turn, renders the EBV-positive malignant cells susceptible to killing by the anti-viral agent ganciclovir. This therapeutic strategy has been successful in early trials. Arginine butyrate, however, has drawbacks as a therapeutic, requiring constant, IV infusion to achieve detectable plasma levels. The development of new, oral agents will allow this therapy to be extended to a larger population of patients and a wider group of diseases. We already have proof-of principal that such orally-active agents can be developed. Our aims from the Phase I STTR were to identify new, long-lived, orally-bioavailable derivatives of our first, prototype drug, Arginine Butyrate, as therapeutics for the therapy of Epstein Barr virus (EBV)-associated malignancies. In this Phase II application, we propose to conduct formal preclinical development studies of a lead new compound, as required by the FDA, to obtain Investigational New Drug Status to begin Phase I clinical trials in humans. The aims of this proposal are: To prepare a medicinal formulation of the sodium salt of ST101, a synthetic SCFAD which ates EBV TK expression, to refine oral dosing-regimens for ST101, to prepare an Investigational New Drug (IND) Application for sodium ST101, and to evaluate additional SCFADs for activity in induction of EBV TK.