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Research Article

Discovery of novel IDO1/TDO2 dual inhibitors: a consensus Virtual screening approach with molecular dynamics simulations, and binding free energy analysis

ORCID Icon & ORCID Icon
Received 30 May 2023, Accepted 06 Mar 2024, Published online: 18 Mar 2024

References

  • Aliebrahimi, S., Montasser Kouhsari, S., Ostad, S. N., Arab, S. S., & Karami, L. (2018). Identification of phytochemicals targeting c-Met kinase domain using consensus docking and molecular dynamics simulation studies. Cell Biochemistry and Biophysics, 76(1-2), 135–145. https://doi.org/10.1007/s12013-017-0821-6
  • Astigiano, S., Morandi, B., Costa, R., Mastracci, L., D'Agostino, A., Ratto, G. B., Melioli, G., & Frumento, G. (2005). Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune escape in human non small cell lung cancer. Neoplasia (New York, N.Y.), 7(4), 390–396. https://doi.org/10.1593/neo.04658
  • Austin, C. J. D., & Rendina, L. M. (2015). Targeting key dioxygenases in tryptophan–kynurenine metabolism for immunomodulation and cancer chemotherapy. Drug Discovery Today, 20(5), 609–617. https://doi.org/10.1016/j.drudis.2014.11.007
  • Baell, J. B., & Holloway, G. A. (2010). New substructure filters for removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for their exclusion in bioassays. Journal of Medicinal Chemistry, 53(7), 2719–2740. https://doi.org/10.1021/jm901137j
  • Bai, Q., Tan, S., Xu, T., Liu, H., Huang, J., & Yao, X. (2021). MolAICal: A soft tool for 3D drug design of protein targets by artificial intelligence and classical algorithm. Briefings in Bioinformatics, 22(3), bbaa161. https://doi.org/10.1093/bib/bbaa161
  • Banerjee, P., Dehnbostel, F. O., & Preissner, R. (2018). Prediction is a balancing act: Importance of sampling methods to balance sensitivity and specificity of predictive models based on imbalanced chemical data sets. Frontiers in Chemistry, 6, 362. https://doi.org/10.3389/fchem.2018.00362
  • Bosshard, H. R., Marti, D. N., & Jelesarov, I. (2004). Protein stabilization by salt bridges: Concepts, experimental approaches and clarification of some misunderstandings. Journal of Molecular Recognition: JMR, 17(1), 1–16. https://doi.org/10.1002/jmr.657
  • Chen, S., Tan, J., & Zhang, A. (2021). The ups, downs and new trends of IDO1 inhibitors. Bioorganic Chemistry, 110, 104815. https://doi.org/10.1016/j.bioorg.2021.104815
  • Cheng, Y., Liu, Y., Xu, J., Zhu, J., Wang, Y., Xin, Y., Wang, Y., Wu, C., Cui, H., Liu, X., Dai, J., Li, Z., Zhang, X., Zhang, J., & Zhang, B. (2021). A phase I study of an IDO inhibitor (SHR9146) plus camrelizumab and in combination with/without apatinib in patients with advanced solid tumors: Safety and efficacy analysis. Journal of Clinical Oncology, 39(15_suppl), 3101–3101. https://doi.org/10.1200/JCO.2021.39.15_suppl.3101
  • Cheong, J. E., Ekkati, A., & Sun, L. (2018). A patent review of IDO1 inhibitors for cancer. Expert Opinion on Therapeutic Patents, 28(4), 317–330. https://doi.org/10.1080/13543776.2018.1441290
  • Chermak, E., Donato, R. D., Lensink, M. F., Petta, A., Serra, L., Scarano, V., Cavallo, L., & Oliva, R. (2016). Introducing a clustering step in a consensus approach for the scoring of protein–protein docking models. PloS One, 11(11), e0166460. https://doi.org/10.1371/journal.pone.0166460
  • Crosignani, S., Bingham, P., Bottemanne, P., Cannelle, H., Cauwenberghs, S., Cordonnier, M., Dalvie, D., Deroose, F., Feng, J. L., Gomes, B., Greasley, S., Kaiser, S. E., Kraus, M., Négrerie, M., Maegley, K., Miller, N., Murray, B. W., Schneider, M., Soloweij, J., … Wythes, M. (2017). Discovery of a novel and selective indoleamine 2,3-dioxygenase (IDO-1) inhibitor 3-(5-fluoro-1 H-indol-3-yl)pyrrolidine-2,5-dione (EOS200271/PF-06840003) and its characterization as a potential clinical candidate. Journal of Medicinal Chemistry, 60(23), 9617–9629. https://doi.org/10.1021/acs.jmedchem.7b00974
  • Cui, G., Lai, F., Wang, X., Chen, X., & Xu, B. (2020). Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as IDO1/TDO dual inhibitors. European Journal of Medicinal Chemistry, 188, 111985. https://doi.org/10.1016/j.ejmech.2019.111985
  • Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717. https://doi.org/10.1038/srep42717
  • Dolusić, E., Larrieu, P., Moineaux, L., Stroobant, V., Pilotte, L., Colau, D., Pochet, L., Van den Eynde, B., Masereel, B., Wouters, J., & Frédérick, R. (2011). Tryptophan 2,3-dioxygenase (TDO) inhibitors 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators. Journal of Medicinal Chemistry, 54(15), 5320–5334. https://doi.org/10.1021/jm2006782
  • Duhalde Vega, M., Aparicio, J. L., Mandour, M. F., & Retegui, L. A. (2020). The autoimmune response elicited by mouse hepatitis virus (MHV-A59) infection is modulated by liver tryptophan-2,3-dioxygenase (TDO). Immunology Letters, 217, 25–30. https://doi.org/10.1016/j.imlet.2019.11.004
  • Ekroos, M., & Sjögren, T. (2006). Structural basis for ligand promiscuity in cytochrome P450 3A4. Proceedings of the National Academy of Sciences of the United States of America, 103(37), 13682–13687. https://doi.org/10.1073/pnas.0603236103
  • Ferreira, L., dos Santos, R., Oliva, G., & Andricopulo, A. (2015). Molecular docking and structure-based drug design strategies. Molecules (Basel, Switzerland), 20(7), 13384–13421. https://doi.org/10.3390/molecules200713384
  • Gonzalez, H., Hagerling, C., & Werb, Z. (2018). Roles of the immune system in cancer: From tumor initiation to metastatic progression. Genes & Development, 32(19-20), 1267–1284. https://doi.org/10.1101/gad.314617.118
  • Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013
  • Hermawan, A., Putri, H., Hanif, N., Fatimah, N., & Prasetio, H. H. (2022). Identification of potential target genes of honokiol in overcoming breast cancer resistance to tamoxifen. Frontiers in Oncology, 12, 1019025. https://doi.org/10.3389/fonc.2022.1019025
  • Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. https://doi.org/10.1016/0263-7855(96)00018-5
  • Hwu, P., Du, M. X., Lapointe, R., Do, M., Taylor, M. W., & Young, H. A. (2000). Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. Journal of İmmunology (Baltimore, Md.: 1950), 164(7), 3596–3599. https://doi.org/10.4049/jimmunol.164.7.3596
  • Iurcu-Mustata, G., Van Belle, D., Wintjens, R., Prévost, M., & Rooman, M. (2001). Role of salt bridges in homeodomains investigated by structural analyses and molecular dynamics simulations. Biopolymers, 59(3), 145–159. https://doi.org/10.1002/1097-0282(200109)59:3
  • Jo, S., Kim, T., Iyer, V. G., & Im, W. (2008). CHARMM-GUI: A web-based graphical user interface for CHARMM. Journal of Computational Chemistry, 29(11), 1859–1865. https://doi.org/10.1002/jcc.20945
  • Jover, R., Bort, R., Gómez-Lechón, M., & Castell, J. V. (2002). Down-regulation of human CYP3A4 by the inflammatory signal interleukin 6: Molecular mechanism and transcription factors involved. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 16(13), 1799–1801. https://doi.org/10.1096/fj.02-0195fje
  • Källberg, E., Wikström, P., Bergh, A., Ivars, F., & Leanderson, T. (2010). Indoleamine 2,3-dioxygenase (IDO) activity influence tumor growth in the TRAMP prostate cancer model. The Prostate, 70(13), 1461–1470. https://doi.org/10.1002/pros.21181
  • Klyushova, L. S., Perepechaeva, M. L., & Grishanova, A. Y. (2022). The role of CYP3A in health and disease. Biomedicines, 10(11), 2686. https://doi.org/10.3390/biomedicines10112686
  • Labadie, B. W., Bao, R., & Luke, J. J. (2019). Reimagining IDO pathway inhibition in cancer immunotherapy via downstream focus on the tryptophan–kynurenine–aryl hydrocarbon axis. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 25(5), 1462–1471. https://doi.org/10.1158/1078-0432.CCR-18-2882
  • Levy, T., Marchand, L., Stroobant, V., Pilotte, L., Van den Eynde, B., Rodriguez, F., & Delfourne, E. (2021). IDO1 and TDO inhibitory evaluation of analogues of the marine pyrroloiminoquinone alkaloids: Wakayin and Tsitsikammamines. Bioorganic & Medicinal Chemistry Letters, 40, 127910. https://doi.org/10.1016/j.bmcl.2021.127910
  • Lewis-Ballester, A., Forouhar, F., Kim, S.-M., Lew, S., Wang, Y., Karkashon, S., Seetharaman, J., Batabyal, D., Chiang, B.-Y., Hussain, M., Correia, M. A., Yeh, S.-R., & Tong, L. (2016). Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. Scientific Reports, 6(1), 35169. https://doi.org/10.1038/srep35169
  • Li, H., Ning, S., Ghandi, M., Kryukov, G. V., Gopal, S., Deik, A., Souza, A., Pierce, K., Keskula, P., Hernandez, D., Ann, J., Shkoza, D., Apfel, V., Zou, Y., Vazquez, F., Barretina, J., Pagliarini, R. A., Galli, G. G., Root, D. E., … Sellers, W. R. (2019). The landscape of cancer cell line metabolism. Nature Medicine, 25(5), 850–860. https://doi.org/10.1038/s41591-019-0404-8
  • Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 24.
  • Liu, J., Ren, J., Yang, K., Chen, S., Yang, X., & Zhao, Q.-S. (2022). Discovery and biological evaluation of tanshinone derivatives as potent dual inhibitors of indoleamine 2, 3-dioxygenase 1 and tryptophan 2, 3-dioxygenase. European Journal of Medicinal Chemistry, 235, 114294. https://doi.org/10.1016/j.ejmech.2022.114294
  • Li, Y., Zhang, S., Wang, R., Cui, M., Liu, W., Yang, Q., & Kuang, C. (2020). Synthesis of novel tryptanthrin derivatives as dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase. Bioorganic & Medicinal Chemistry Letters, 30(11), 127159. https://doi.org/10.1016/j.bmcl.2020.127159
  • Long, G. V., Dummer, R., Hamid, O., Gajewski, T., Caglevic, C., Dalle, S., Arance, A., Carlino, M. S., Grob, J.-J., Kim, T. M., Demidov, L. V., Robert, C., Larkin, J. M. G., Anderson, J., Maleski, J. E., Jones, M. M., Diede, S. J., & Mitchell, T. C. (2018). Epacadostat (E) plus pembrolizumab (P) versus pembrolizumab alone in patients (pts) with unresectable or metastatic melanoma: Results of the phase 3 ECHO-301/KEYNOTE-252 study. Journal of Clinical Oncology, 36(15_suppl), 108–108. https://doi.org/10.1200/JCO.2018.36.15_suppl.108
  • Maia, E. H. B., Assis, L. C., de Oliveira, T. A., da Silva, A. M., & Taranto, A. G. (2020). Structure-based virtual screening: From classical to artificial intelligence. Frontiers in Chemistry, 8, 343. https://doi.org/10.3389/fchem.2020.00343
  • Mammoli, A., Bianconi, E., Ruta, L., Riccio, A., Bigiotti, C., Souma, M., Carotti, A., Rossini, S., Suvieri, C., Pallotta, M. T., Grohmann, U., Camaioni, E., & Macchiarulo, A. (2022). Critical assessment of a structure-based screening campaign for IDO1 inhibitors: Tips and pitfalls. International Journal of Molecular Sciences, 23(7), 3981. https://doi.org/10.3390/ijms23073981
  • Mansfield, A. S., Heikkila, P. S., Vaara, A. T., von Smitten, K. A., Vakkila, J. M., & Leidenius, M. H. (2009). Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer. BMC Cancer, 9(1) https://doi.org/10.1186/1471-2407-9-231
  • Mbaye, M. N., Hou, Q., Basu, S., Teheux, F., Pucci, F., & Rooman, M. (2019). A comprehensive computational study of amino acid interactions in membrane proteins. Scientific Reports, 9(1), 12043. https://doi.org/10.1038/s41598-019-48541-2
  • Meuzelaar, H., Vreede, J., & Woutersen, S. (2016). Influence of Glu/Arg, Asp/Arg, and Glu/Lys salt bridges on α-helical stability and folding kinetics. Biophysical Journal, 110(11), 2328–2341. https://doi.org/10.1016/j.bpj.2016.04.015
  • Mondal, A., Smith, C., DuHadaway, J. B., Sutanto-Ward, E., Prendergast, G. C., Bravo-Nuevo, A., & Muller, A. J. (2016). IDO1 is an integral mediator of inflammatory neovascularization. EBioMedicine, 14, 74–82. https://doi.org/10.1016/j.ebiom.2016.11.013
  • O’Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An open chemical toolbox. Journal of Cheminformatics, 3(1), 33. https://doi.org/10.1186/1758-2946-3-33
  • Parr, B. T., Pastor, R., Sellers, B. D., Pei, Z., Jaipuri, F. A., Castanedo, G. M., Gazzard, L., Kumar, S., Li, X., Liu, W., Mendonca, R., Pavana, R. K., Potturi, H., Shao, C., Velvadapu, V., Waldo, J. P., Wu, G., Yuen, P., Zhang, Z., … Liu, Y. (2020). Implementation of the CYP Index for the design of selective tryptophan-2,3-dioxygenase inhibitors. ACS Medicinal Chemistry Letters, 11(4), 541–549. https://doi.org/10.1021/acsmedchemlett.0c00004
  • Pham, K. N., Lewis-Ballester, A., & Yeh, S.-R. (2019). Structural basis of inhibitor selectivity in human indoleamine 2,3-dioxygenase 1 and tryptophan dioxygenase. Journal of the American Chemical Society, 141(47), 18771–18779. https://doi.org/10.1021/jacs.9b08871
  • Phillips, J. C., Hardy, D. J., Maia, J. D. C., Stone, J. E., Ribeiro, J. V., Bernardi, R. C., Buch, R., Fiorin, G., Hénin, J., Jiang, W., McGreevy, R., Melo, M. C. R., Radak, B. K., Skeel, R. D., Singharoy, A., Wang, Y., Roux, B., Aksimentiev, A., Luthey-Schulten, C., … Tajkhorshid, E. (2020). Scalable molecular dynamics on CPU and GPU architectures with NAMD. The Journal of Chemical Physics, 153(4), 044130. https://doi.org/10.1063/5.0014475
  • Pilotte, L., Larrieu, P., Stroobant, V., Colau, D., Dolusic, E., Frédérick, R., De Plaen, E., Uyttenhove, C., Wouters, J., Masereel, B., & Van den Eynde, B. J. (2012). Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proceedings of the National Academy of Sciences of the United States of America, 109(7), 2497–2502. https://doi.org/10.1073/pnas.1113873109
  • Platten, M., von Knebel Doeberitz, N., Oezen, I., Wick, W., & Ochs, K. (2014). Cancer immunotherapy by targeting IDO1/TDO and their downstream effectors. Frontiers in İmmunology, 5, 673. https://doi.org/10.3389/fimmu.2014.00673
  • Poli, G., Martinelli, A., & Tuccinardi, T. (2016). Reliability analysis and optimization of the consensus docking approach for the development of virtual screening studies. Journal of Enzyme İnhibition and Medicinal Chemistry, 31(sup2), 167–173. https://doi.org/10.1080/14756366.2016.1193736
  • Prendergast, G. C., Malachowski, W. J., Mondal, A., Scherle, P., & Muller, A. J. (2018). Indoleamine 2,3-dioxygenase and its therapeutic inhibition in cancer. International Review of Cell and Molecular Biology, 336, 175–203. https://doi.org/10.1016/bs.ircmb.2017.07.004
  • Röhrig, U. F., Majjigapu, S. R., Vogel, P., Zoete, V., & Michielin, O. (2015). Challenges in the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. Journal of Medicinal Chemistry, 58(24), 9421–9437. https://doi.org/10.1021/acs.jmedchem.5b00326
  • Salter, M., Hazelwood, R., Pogson, C. I., Iyer, R., & Madge, D. J. (1995). The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat. Biochemical Pharmacology, 49(10), 1435–1442. https://doi.org/10.1016/0006-2952(95)00006-L
  • Selvan, S. R., Dowling, J. P., Kelly, W. K., & Lin, J. (2016). Indoleamine 2, 3-dioxygenase (IDO): Biology and target in cancer immunotherapies. Current Cancer Drug Targets, 16(9), 755–764. https://doi.org/10.2174/1568009615666151030102250
  • Sevrioukova, I. (2019). Interaction of human drug-metabolizing CYP3A4 with small inhibitory molecules. Biochemistry, 58(7), 930–939. https://doi.org/10.1021/acs.biochem.8b01221
  • Sevrioukova, I. F., & Poulos, T. L. (2010). Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proceedings of the National Academy of Sciences of the United States of America, 107(43), 18422–18427. https://doi.org/10.1073/pnas.1010693107
  • Sharom, F. J. (2011). The P-glycoprotein multidrug transporter. Essays in Biochemistry, 50(1), 161–178. https://doi.org/10.1042/bse0500161
  • Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J. M., Desrichard, A., Walsh, L. A., Postow, M. A., Wong, P., Ho, T. S., Hollmann, T. J., Bruggeman, C., Kannan, K., Li, Y., Elipenahli, C., Liu, C., Harbison, C. T., Wang, L., Ribas, A., Wolchok, J. D., & Chan, T. A. (2014). Genetic basis for clinical response to CTLA-4 blockade in melanoma. The New England Journal of Medicine, 371(23), 2189–2199. https://doi.org/10.1056/NEJMoa1406498
  • Soler, M. F., Abaurrea, A., Azcoaga, P., Araujo, A. M., & Caffarel, M. M. (2023). New perspectives in cancer immunotherapy: Targeting IL-6 cytokine family. Journal for ImmunoTherapy of Cancer, 11(11), e007530. https://doi.org/10.1136/jitc-2023-007530
  • Sterling, T., & Irwin, J. J. (2015). ZINC 15 – Ligand discovery for everyone. Journal of Chemical İnformation and Modeling, 55(11), 2324–2337. https://doi.org/10.1021/acs.jcim.5b00559
  • Tang, K., Wu, Y.-H., Song, Y., & Yu, B. (2021). Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy. Journal of Hematology & Oncology, 14(1), 68. https://doi.org/10.1186/s13045-021-01080-8
  • Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., Leming, P. D., Spigel, D. R., Antonia, S. J., Horn, L., Drake, C. G., Pardoll, D. M., Chen, L., Sharfman, W. H., Anders, R. A., … Sznol, M. (2012). Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. The New England Journal of Medicine, 366(26), 2443–2454. https://doi.org/10.1056/NEJMoa1200690
  • Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
  • Tuccinardi, T., Poli, G., Romboli, V., Giordano, A., & Martinelli, A. (2014). Extensive consensus docking evaluation for ligand pose prediction and virtual screening studies. Journal of Chemical İnformation and Modeling, 54(10), 2980–2986. https://doi.org/10.1021/ci500424n
  • van Baren, N., & Van den Eynde, B. J. (2015). Tryptophan-degrading enzymes in tumoral immune resistance. Frontiers in İmmunology, 6, 34. https://doi.org/10.3389/fimmu.2015.00034
  • Vázquez, J., López, M., Gibert, E., Herrero, E., & Luque, F. J. (2020). Merging ligand-based and structure-based methods in drug discovery: An overview of combined virtual screening approaches. Molecules (Basel, Switzerland), 25(20), 4723. https://doi.org/10.3390/molecules25204723
  • Vilar, S., Cozza, G., & Moro, S. (2008). Medicinal chemistry and the molecular operating environment (MOE): Application of QSAR and molecular docking to drug discovery. Current Topics in Medicinal Chemistry, 8(18), 1555–1572. https://doi.org/10.2174/156802608786786624
  • Weng, T., Qiu, X., Wang, J., Li, Z., & Bian, J. (2018). Recent discovery of indoleamine-2,3-dioxygenase 1 inhibitors targeting cancer immunotherapy. European Journal of Medicinal Chemistry, 143, 656–669. https://doi.org/10.1016/j.ejmech.2017.11.088
  • Winters, M., DuHadaway, J. B., Pham, K. N., Lewis-Ballester, A., Badir, S., Wai, J., Sheikh, E., Yeh, S.-R., Prendergast, G. C., Muller, A. J., & Malachowski, W. P. (2019). Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase. European Journal of Medicinal Chemistry, 162, 455–464. https://doi.org/10.1016/j.ejmech.2018.11.010
  • Wu, Y., Xu, T., Liu, J., Ding, K., & Xu, J. (2017). Structural insights into the binding mechanism of IDO1 with hydroxylamidine based inhibitor INCB14943. Biochemical and Biophysical Research Communications, 487(2), 339–343. https://doi.org/10.1016/j.bbrc.2017.04.061
  • Yang, L., Chen, Y., He, J., Njoya, E. M., Chen, J., Liu, S., Xie, C., Huang, W., Wang, F., Wang, Z., Li, Y., & Qian, S. (2019). 4,6-Substituted-1H-indazoles as potent IDO1/TDO dual inhibitors. Bioorganic & Medicinal Chemistry, 27(6), 1087–1098. https://doi.org/10.1016/j.bmc.2019.02.014
  • Yang, D., Zhang, S., Fang, X., Guo, L., Hu, N., Guo, Z., Li, X., Yang, S., He, J. C., Kuang, C., & Yang, Q. (2019). N-Benzyl/aryl substituted tryptanthrin as dual inhibitors of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase. Journal of Medicinal Chemistry, 62(20), 9161–9174. https://doi.org/10.1021/acs.jmedchem.9b01079
  • Zhang, Y., Hu, Z., Zhang, J., Ren, C., & Wang, Y. (2022). Dual-target inhibitors of indoleamine 2, 3 dioxygenase 1 (Ido1): A promising direction in cancer immunotherapy. European Journal of Medicinal Chemistry, 238, 114524. https://doi.org/10.1016/j.ejmech.2022.114524
  • Zhang, Y., Li, Y., Chen, X., Chen, X., Chen, C., Wang, L., Dong, X., Wang, G., Gu, R., Li, F., Han, F., & Chen, D. (2022). Discovery of 1-(hetero)aryl-β-carboline derivatives as IDO1/TDO dual inhibitors with antidepressant activity. Journal of Medicinal Chemistry, 65(16), 11214–11228. https://doi.org/10.1021/acs.jmedchem.2c00677
  • Zhao, Y., Sun, J., Li, Y., Zhou, X., Zhai, W., Wu, Y., Chen, G., Gou, S., Sui, X., Zhao, W., Qiu, L., Yao, Y., Sun, Y., Chen, C., Qi, Y., & Gao, Y. (2021). Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway. Acta Pharmaceutica Sinica. B, 11(9), 2835–2849. https://doi.org/10.1016/j.apsb.2021.03.009

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