molecules of the month

NLG802 is a prodrug of the IDO1 inhibitor indoximod with significantly enhanced oral exposure. Both the acid and amine functionalities of indoximod are protected as an ethyl ester and leucine amide, respectively. Prodrugs are generally difficult to develop so it’s interesting that two biotransformations are employed. The molecule is first cleaved to the carboxylic acid by carboxyesterases CES1b and CES1c, which is then further cleaved by unidentified peptidases to release indoximod.