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CHENG Yulan, MEN Jinxia, ZHOU Jinpei, ZHANG Huibin. Advances in indoleamine 2, 3-dioxygenase 1 inhibitors[J]. Journal of China Pharmaceutical University, 2017, 48(3): 361-370. DOI: 10.11665/j.issn.1000-5048.20170318
Citation: CHENG Yulan, MEN Jinxia, ZHOU Jinpei, ZHANG Huibin. Advances in indoleamine 2, 3-dioxygenase 1 inhibitors[J]. Journal of China Pharmaceutical University, 2017, 48(3): 361-370. DOI: 10.11665/j.issn.1000-5048.20170318
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Advances in indoleamine 2, 3-dioxygenase 1 inhibitors

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  • Indoleamine 2, 3-dioxygenase 1(IDO1)is the rate-limiting enzyme which catalyses the metabolism of L-tryptophan(L-Trp)in the kynurenine pathway. It is overexpressed in many tumor cells and antigen presenting cells. This enzyme inhibits local immune response and supports tumor cells to evade immune surveillance by depleting L-Trp and producing kynurenine metabolites, thus, it is an important target for cancer immunotherapy. There are several IDO1 inhibitors with different scarfold under investigation, three of which have already entered clinical stage. The role of IDO1 in tumor immune tolerance and the research progress on IDO1 inhibitors in recent years are summarized in this paper.
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  • [1]
    Topalian SL, Drake CG, Pardoll DM, et al. Immune checkpoint blockade:a common denominator approach to cancer therapy[J].Cancer Cell,2015,27(4):450-461.
    [2]
    Jena B,Moyes JS,Huls H,et al.Driving CAR-based T-cell therapy to success[J].Curr Hematol Malig Rep,2014,9(1):50-56.
    [3]
    Rosenberg SA. Raising the bar: the curative potential of human caner immunotherapy[J].Sci Transl Med,2012,4(127):844-844.
    [4]
    Spranger S, Koblish HK, Horton B, et al. Mechanism of tumor rejection with doublets of CTLA-4,PD-1/PD-L1,or IDO blockade involves restored IL-2 production and proliferation of CD8+ T cells directly within the tumor microenvironment[J].J Immunother Cancer,2014,2(1):1-14.
    [5]
    Vécsei L, Szalárdy L, Fülop F, et al. Kynurenines in the CNS:recent advances and new questions[J].Nat Rev Drug Discov,2013,12(1):64-82.
    [6]
    Richard DM,Dawes MA,Mathias CW,et al.L-Tryptophan:basic metabolic functions,behavioral research and therapeutic indications[J].Int J Tryptophan Res,2009,2(2):45-60.
    [7]
    Beadle GW,Mitchell HK,Nyc JF.Kynurenine as an intermediate in the formation of nicotinic acid from tryptophane by neurospora[J].Proc Natl Acad of Sci U S A,1947,33(6):155-158.
    [8]
    Dounay AB,Tuttle JB,Verhoest PR.Challenges and opportunities in the discovery of new therapeutics targeting the kynurenine pathway[J].J Med Chem,2015,58(22):8762-8782.
    [9]
    Barth H,Raghuraman S.Persistent infectious diseases say -IDO.Role of indoleamine-2,3-dioxygenase in disease pathogenesis and implications for therapy[J].Crit Rev Microbiol,2014,40(4):360-368.
    [10]
    Théate I,van Baren N,Pilotte L,et al.Extensive profiling of the expression of the indoleamine 2,3-dioxygenase 1 protein in normal and tumoral human tissues[J].Cancer Immunol Res,2015,3(2):161-172.
    [11]
    Godin-Ethier J,Hanafi LA,Piccirillo CA,et al.Indoleamine 2,3-dioxygenase expression in human cancers:clinical and immunologic perspectives[J].Clin Cancer Res,2011,17(22):6985-6991.
    [12]
    Li M,Bolduc AR,Hoda MN,et al.The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma[J].J Immunother Cancer,2014,2(1):1-13.
    [13]
    Pilotte L, Larrieu P, Stroobant V, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase[J].Proc Natl Acad Sci U S A,2012,109(7):2497-2502.
    [14]
    Ball HJ,Sanchez-Perez A,Weiser S,et al.Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice[J].Gene,2007,396(1):203-213.
    [15]
    van Baren N, Van den Eynde BJ. Tumoral immune resistance mediated by enzymes that degrade tryptophan[J].Cancer Immunol Res,2015,3(9):978-985.
    [16]
    Munn DH,Sharma MD,Baban B,et al.GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase[J].Immunity,2005,22(5):633-642.
    [17]
    Metz R,Rust S,Duhadaway JB,et al.IDO inhibits a tryptophan sufficiency signal that stimulates mTOR:a novel IDO effector pathway targeted by D-1-methyl-tryptophan[J].Oncoimmunology,2012,1(9):1460-1468.
    [18]
    Munn DH,Mellor AL.Indoleamine 2,3 dioxygenase and metabolic control of immune responses[J].Trends Immunol,2013,34(3):137-143.
    [19]
    Qian S,Zhang M,Chen Q,et al.IDO as a drug target for cancer immunotherapy:recent developments in IDO inhibitors discovery[J].RSC Adv,2016,6(9):7575-7581.
    [20]
    van Baren N, Van den Eynde BJ. Tumoral immune resistance mediated by enzymes that degrade tryptophan[J].Cancer Immunol Res,2015,3(9):978-985.
    [21]
    Sakamuro D,Elliott KJ,Wechslerreya R,et al.BIN1 is a novel MYC-interacting protein with features of a tumour suppressor[J].Nat Genet,1996,14(1):69-77.
    [22]
    Jia Y,Wang H,Wang Y,et al.Low expression of Bin1,along with high expression of IDO in tumor tissue and draining lymph nodes,are predictors of poor prognosis for esophageal squamous cell cancer patients[J].Int J Cancer,2015,137(5):1095-1106.
    [23]
    Muller AJ, Duhadaway JB, Donover PS, et al. Inhibition of indoleamine 2,3-dioxygenase,an immunoregulatory target of the cancer suppression gene Bin1,potentiates cancer chemotherapy[J].Nat Med,2005,11(3):312-319.
    [24]
    Rohrig UF,Majjigapu SR,Vogel P,et al.Challenges in the discovery of indoleamine 2,3-dioxygenase 1(IDO1)inhibitors[J].J Med Chem,2015,58(24):9421-9437.
    [25]
    Soliman HH,Minton SE,Han HS,et al.A phase I study of indoximod in patients with advanced malignancies[J].Oncotarget,2016,7(16):22928-22938.
    [26]
    Sugimoto H, Oda S, Otsuki T, et al. Crystal structure of human indoleamine 2,3-dioxygenase:catalytic mechanism of O2 incorporation by a heme-containing dioxygenase[J].Proc Natl Acad Sci U S A,2006,103(8):2611-2616.
    [27]
    Tojo S,Kohno T,Tanaka T,et al.Crystal structures and structure-activity relationships of imidazothiazole derivatives as IDO1 inhibitors[J].ACS Med Chem Lett,2014,5(10):1119-1123.
    [28]
    Mautino MR,Kumar S,Jaipuri FA,et al.Imidazole derivatives as IDO inhibitors:IN,2011056652 A1[P].2011-05-12[2016-07-17] .
    [29]
    Mautino MR,Kumar S,Waldo J,et al.Fused imidazole derivatives as IDO inhibitors:IN,2012142237 A1[P].2012-10-18[2016-07-17] .
    [30]
    Mautino MR,Jaipuri FA,Waldo J,et al.Abstract 491:NLG919,a novel indoleamine-2,3-dioxygenase(IDO)-pathway inhibitor drug candidate for cancer therapy[J].Cancer Res,2013,73(8):491-491.
    [31]
    Nayak A,Hao Z,Sadek R,et al.Phase 1a study of the safety,pharmacokinetics,and pharmacodynamics of GDC-0919 in patients with recurrent/advanced solid tumors[J].Eur J Cancer,2015,51(1):S69-S69.
    [32]
    Rahrig UF, Awad L, Grosdidier A, et al. Rational design of indoleamine 2,3-dioxygenase inhibitors[J].J Med Chem,2010,53(3):1172-1189.
    [33]
    Huang Q,Zheng M,Yang S,et al.Structure-activity relationship and enzyme kinetic studies on 4-aryl-1H-1,2,3-triazoles as indoleamine 2,3-dioxygenase(IDO)inhibitors[J].Eur J Med Chem,2011,46(11):5680-5687.
    [34]
    Rohrig UF,Majjigapu SR,Grosdidier A,et al.Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition[J].J Med Chem,2012,55(11):5270-5290.
    [35]
    Boyall D,Davis C,Dodd J,et al,Compounds useful as inhibitors of indoleamine 2,3-dioxygenase:IN,2014081689 A1[P].2014-05-30[2016-07-17] .
    [36]
    Yue EW,Douty B,Wayland B,et al.Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model[J].J Med Chem,2009,52(52):7364-7367.
    [37]
    Combs AP, Yue EW, Sparks RB, et al, 1, 2, 5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase:IN,2010005958 A1[P].2010-01-14[2016-07-17] .
    [38]
    Gangadhar TC,Hamid O,Smith DC,et al.Preliminary results from a Phase I/II study of epacadostat(incb024360)in combination with pembrolizumab in patients with selected advanced cancers[J].J Immunothe Cancer,2015,3(S2):1-2.
    [39]
    Paul S,Roy A,Deka SJ,et al.Nitrobenzofurazan derivatives of N′-hydroxyamidines as potent inhibitors of indoleamine-2,3-dioxygenase 1[J].Eur J Med Chem,2016,121(10):364-375.
    [40]
    Jaen JC,Osipov M,Powers JP,et al.Immunoregulatory agents:IN,2015188085 A1[P].2015-12-10[2016-07-17] .
    [41]
    Beck HP,Jaen JC,Osipov M,et al.Immunoregulatory agents:IN,2016073774 A2[P].2016-05-12[2016-07-17] .
    [42]
    Beck HP,Jaen JC,Osipov M,et al.Immunoregulatory agents:IN,2016073770 A1[P].2016-05-12[2016-07-17] .
    [43]
    Beck HP,Jaen JC,Osipov M,et al.Immunoregulatory agents:IN,2016073738 A2[P].2016-05-12[2016-07-17] .
    [44]
    Cheng MF, Hung MS, Song JS, et al. Discovery and structure-activity relationships of phenyl benzenesulfonylhydrazides as novel indoleamine 2,3-dioxygenase inhibitors[J].Bioorg Med Chem Lett,2014,24(15):3403-3406.
    [45]
    Lin SY,Yeh TK,Kuo CC,et al.Phenyl benzenesulfonylhydrazides exhibit selective indoleamine 2,3-dioxygenase inhibition with potent in vivo pharmacodynamic activity and antitumor efficacy[J].J Med Chem,2016,59(1):419-430.
    [46]
    Banergee M,Middya S,Shrivastava R,et al.Aminonitriles as kynurenine pathway inhibitors:IN,2014141110 A2[P].2014-09-18[2016-07-17] .
    [47]
    Banergee M,Middya S,Shrivastava R,et al.Inhibitors of the kynurenine pathway:IN,2014186035 A1[P].2014-11-20[2016-07-17] .
    [48]
    Middya S, Yadav DB, Shrivastava R, et al, Novel iminonitrile derivatives:IN,2016027241 A1[P].2016-02-25[2016-07-17] .
    [49]
    Cowley P, Wise A. Inhibitors of trytophan 2, 3-dioxygenase or indoleamine 2,3-dioxygenase:IN,2016071283 A1[P].2016-05-12[2016-07-17] .
    [50]
    Cowley P,Wise A.Pharmaceutical compound:IN,2016071293 A2[P].2016-05-12[2016-07-17] .
    [51]
    Cowley P,Wise A.Pharmaceutical compound:IN,2016026772 A1[P].2016-02-25[2016-07-17] .
    [52]
    Cowley P,Wise A.Indole derivatives for use in medicine:IN,2015150097 A1[P].2015-10-08[2016-07-17] .
    [53]
    Cowley P,Wise A.Pharmaceutical compound:IN,2015082499 A2[P].2015-06-11[2016-07-17] .
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