Background:

NLG919 is a novel and orally-bioavailable small-molecule inhibitor of indoleamine 2,3-dioxygenase (IDO) pathway, a crucial pathway involved in allergic inflammation that mediates immunosuppressive effects through metabolization of tryptophan (Trp) to kynurenine and affects differentiation and proliferation of T cells through inducing downstream signaling via GCN2, mTOR and AHR, with values of inhibition constantK_iand half maximal effective concentration EC₅₀of 7 nM and 75 nM respectively. Due to the established correlation of IDO pathway with various malignancies, the IDO pathway inhibition as well as its desirable pharmacological and biological properties potentiates NLG919 to be used for the treatment of immunosuppression associated with cancer.

Reference

Mario R. Mautino, Firoz A. Jaipuri, Jesse Waldo, Sanjeev Kumar, James Adams, Clarissa Van Allen, Agnieszka Marcinowicz-Flick, David Munn, Nicholas Vahanian, Charles J. Link. NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 491. doi:10.1158/1538-7445.AM2013-491