indoximod and 1-methyltryptophan

A series of different prodrugs of indoximod, including estesrs and peptide amides were synthesized with the aim of improving its oral bioavailability in humans. The pharmacokinetics of prodrugs that were stable in buffers, plasma and simulated gastric and intestinal fluids was first assessed in rats after oral dosing in solution or in capsule formulation. Two prodrugs that produced the highest exposure to indoximod in rats were further tested in Cynomolgus monkeys, a species in which indoximod has oral bioavailability of 6-10% and an equivalent dose-dependent exposure profile as humans. NLG802 was selected as the clinical development candidate after increasing oral bioavailability (>5-fold), C

Topics: Administration, Oral; Animals; Antineoplastic Agents; Apoptosis; Biological Availability; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Compounding; Drug Screening Assays, Antitumor; Haplorhini; Humans; Intestinal Absorption; Mice; Molecular Conformation; Neoplasms; Prodrugs; Rats; Tryptophan