indoximod

Indoximod (NLG-8189) is a methylated tryptophan with immune checkpoint inhibitory activity. Indoximod inhibits the enzyme indoleamine 2, 3-dioxygenase (IDO), which degrades the essential amino acid tryptophan, and may increase or maintain tryptophan levels important to T cell function. Tryptophan depletion is associated with immunosuppression involving T cell arrest and anergy.

(S)-Indoximod (L-Abrine) exhibits inhibition of rabbit small intestine indoleamine 2, 3-dioxygenase, competitive inhibition of IDO, reduction of Foxp3 protein expression in tumor of C57BL 6 mouse allografted with mouse LLC cells at 200 mg kg, induction of IDO1 protein expression in tumor of C57BL 6 mouse allografted with mouse LLC cells at 200 mg kg, antitumor activity against mouse LLC cells allografted in C57BL 6 mouse, antiproliferative activity against mouse LLC cells at 50 uM.

(Rac)-Indoximod (1-Methyl-DL-tryptophan) is a potent inhibitor of indoleamine 2,3-dioxygenase (IDO). Combined treatment with IFN-γ and (Rac)-Indoximod significantly suppresses the activity of α-SMA-expressing human cardiac myofibroblasts (hCMs) and promotes apoptosis by up-regulating the genes IRF-1, Fas, and FasL, effectively improving cardiac fibrosis[1].

NLG802 is a prodrug of indoximod, serving as an orally active inhibitor of indoleamine 2,3-dioxygenase (IDO).

NLG802 is an orally bioavailable prodrug of indoximod, a methylated tryptophan, with immune checkpoint inhibitory and antineoplastic activities. Upon oral administration, the indoximod prodrug NLG802 is converted to indoximod. Indoximod targets, binds to and inhibits the enzyme indoleamine 2,3-dioxygenase (IDO; IDO1), which converts the essential amino acid tryptophan into the immunosuppressive metabolite kynurenine. By increasing tryptophan levels and decreasing kynurenine levels, indoximod restores and promotes the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T lymphocytes, and causes a reduction in tumor-associated regulatory T cells (Tregs).