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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.
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