LY-3381916

Background Information:

LY-3381916 is an orally available, potent and selective inhibitor of
indoleamine 2,3-dioxygenase 1 (IDO-1) (IC50 = 7 nM on Cell-based, newly
synthesized IDO-1 lacking heme), with potential immunomodulating and
antineoplastic activities. Upon administration, IDO1 inhibitor LY3381916
specifically targets and binds to IDO1, a cytosolic enzyme responsible
for the oxidation of the amino acid tryptophan into the
immunosuppressive metabolite kynurenine. By inhibiting IDO1 and
decreasing kynurenine in tumor cells, LY3381916 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).
Activation of the immune system, which is suppressed in many cancers,
may induce a cytotoxic T-lymphocyte (CTL) response against the
IDO1-expressing tumor cells, thereby inhibiting the growth of
IDO1-expressing tumor cells. IDO1, overexpressed by multiple tumor cell
types, plays an important role in immunosuppression. Tryptophan
depletion inhibits T-lymphocyte proliferation and activation, and
subsequently suppresses the immune system.

Reference:

1. Frank C. Dorsey, et al, Identification and characterization of the
IDO1 inhibitor LY3381916, In: Proceedings of the American Association
for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL.
Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl): Abstract nr 5245.

APIM050043: LY3381916

CAS No.: 2166616-75-5.
Molecular Formula: C23H25FN2O3.
Molecular Weight: 396.5.
Purity: >99.5% by Achiral and Chiral HPLCs.
QC: Achiral and Chiral HPLCs, MS, 1H-NMRs, and Quantitative Elemental Analysis Report.
Solubility: Refer to Certification of Analysis.
Storage: Refer to Certification of Analysis.