Current state on tryptophan 2,3-dioxygenase inhibitors: a patent review

References

• Sainio E-L, Pulkki K, Young SN. L-Tryptophan: biochemical, nutritional and pharmacological aspects. Amino acids. Springer-Verlag; 1996;10(1):21-47.
   Google Scholar
• Tan P, Bharath A. Manipulation of indoleamine 2,3 dioxygenase; a novel therapeutic target for treatment of diseases. Expert Opin Ther Targets. 2009;13:987–1012.
   PubMed Web of Science ®Google Scholar
• Fallarino F, Grohmann U, Vacca C, et al. T cell apoptosis by tryptophan catabolism. Cell Death Differ. 2002;9:1069–1077.
   PubMed Web of Science ®Google Scholar
• Grohmann U, Fallarino F, Puccetti P. Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol. 2003;24:242–248.
   PubMed Web of Science ®Google Scholar
• Routy J-P, Routy B, Graziani GM, et al. The kynurenine pathway is a double-edged sword in immune-privileged sites and in cancer: implications for immunotherapy. Int J Tryptophan Res. 2016;9:67–77.
   PubMed Web of Science ®Google Scholar
• Pilotte L, Larrieu P, Stroobant V, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci. 2012;109:2497–2502.
   PubMed Web of Science ®Google Scholar
• Kegel ME, Bhat M, Skogh E, et al. Imbalanced kynurenine pathway in schizophrenia. Int J Tryptophan Res. 2014;7:15–22.
   PubMedGoogle Scholar
• Myint A-M, Schwarz MJ, Müller N. The role of the kynurenine metabolism in major depression. J Neural Transm. 2012;119:245–251.
   PubMed Web of Science ®Google Scholar
• Baran H, Jellinger K, Deecke L. Kynurenine metabolism in Alzheimer’s disease. J Neural Transm. 1999;106:165–181.
   PubMed Web of Science ®Google Scholar
• Ball HJ, Jusof FF, Bakmiwewa SM, et al. Tryptophan-catabolizing enzymes – party of three. Front Immunol. 2014;5:1–10.
   PubMed Web of Science ®Google Scholar
• Ogawa T, Matson WR, Beal MF, et al. Kynurenine pathway abnormalities in Parkinson’s disease. Neurology. 1992;42:1702–1706.
   PubMed Web of Science ®Google Scholar
• Guillemin GJ, Brew BJ. Implications of the kynurenine pathway and quinolinic acid in Alzheimer’s disease. Redox Rep. 2002;7:199–206.
   PubMed Web of Science ®Google Scholar
• Hayaishi O. Properties and function of indoleamine 2,3-dioxygenase. J Biochem. 1976;79:13P–21P.
   PubMed Web of Science ®Google Scholar
• Yamazaki F, Kuroiwa T, Takikawa O, et al. Human indolylamine 2,3-dioxygenase. Its tissue distribution, and characterization of the placental enzyme. Biochem J. 1985;230:635–638.
   PubMed Web of Science ®Google Scholar
• Terness P, Bauer TM, Röse L, et al. Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med. 2002;196:447–457.
   PubMed Web of Science ®Google Scholar
• Taylor MW, Feng GS. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991;5:2516–2522.
   PubMed Web of Science ®Google Scholar
• Opitz CA, Litzenburger UM, Lutz C, et al. Toll-like receptor engagement enhances the immunosuppressive properties of human bone marrow-derived mesenchymal stem cells by inducing indoleamine-2,3-dioxygenase-1 via interferon-β and protein kinase R. Stem Cells. 2009;27:909–919.
   PubMed Web of Science ®Google Scholar
• Munn DH, Zhou M, Attwood JT, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281:1191–1193.
   PubMed Web of Science ®Google Scholar
• Moffett JR, Namboodiri MA. Tryptophan and the immune response. Immunol Cell Biol. 2003;81:247–265.
   PubMed Web of Science ®Google Scholar
• Badawy AA-B. Tryptophan metabolism, disposition and utilization in pregnancy. Biosci Rep. 2015;35(5).
   Web of Science ®Google Scholar
• Badawy AA-B, Namboodiri AMA, Moffett JR. The end of the road for the tryptophan depletion concept in pregnancy and infection. Clin Sci (Lond). 2016;130:1327–1333.
   PubMed Web of Science ®Google Scholar
• Uyttenhove C, Pilotte L, Théate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269–1274.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Kang SA, Mukherjee T, et al. Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme enzyme involved in tryptophan catabolism and in quinolinate biosynthesis. Biochemistry. 2007;46:145–155.
   PubMed Web of Science ®Google Scholar
• Lewis-Ballester A, Forouhar F, Kim S-M, et al. Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. Sci Rep. 2016;6:35169.
   PubMed Web of Science ®Google Scholar
• Miller CL, Llenos IC, Dulay JR, et al. Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Neurobiol Dis. 2004;15:618–629.
   PubMed Web of Science ®Google Scholar
• Breda C, Sathyasaikumar KV, Sograte Idrissi S, et al. Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites. Proc Natl Acad Sci U S A. 2016;113:201604453.
   Web of Science ®Google Scholar
• Lanz TV, Williams SK, Stojic A, et al. Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis. Sci Rep. 2017 [cited 2018 Sep 17];7:41271.
   PubMed Web of Science ®Google Scholar
• Nakamura T, Niimi S, Nawa K, et al. Multihormonal regulation of transcription of the tryptophan 2,3-dioxygenase gene in primary cultures of adult rat hepatocytes with special reference to the presence of a transcriptional protein mediating the action of glucocorticoids. J Biol Chem. 1987;262:727–733.
   PubMed Web of Science ®Google Scholar
• Badawy AA-B. Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects. Int J Tryptophan Res. 2017;10(2017):1178646917691938.
   Google Scholar
• Salter M, Hazelwood R, Pogson CI, et al. The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat. Biochem Pharmacol. 1995;49:1435–1442.
   PubMed Web of Science ®Google Scholar
• Opitz CA, Litzenburger UM, Sahm F, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature. 2011;478:197–203.
   PubMed Web of Science ®Google Scholar
• Dolušić E, Larrieu P, Moineaux L, et al. Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators. J Med Chem. 2011;54:5320–5334.
   PubMed Web of Science ®Google Scholar
• Dolusic E. Indoleamine 2,3-dioxygenase inhibitors : a patent review. Expert Opin Ther Pat. 2013;23:1367–1381.
   PubMed Web of Science ®Google Scholar
• Cheong JE, Ekkati A, Sun L. A patent review of IDO1 inhibitors for cancer. Expert Opin Ther Pat. 2018;28:317–330.
   PubMed Web of Science ®Google Scholar
• Takikawa O, Kuroiwa T, Yamazaki F, et al. Mechanism of interferon-gamma action. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity. J Biol Chem. 1988;263:2041–2048.
   PubMed Web of Science ®Google Scholar
• Röhrig UF, Majjigapu SR, Vogel P, et al. Challenges in the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. J Med Chem. 2015;58:9421–9437.
   PubMed Web of Science ®Google Scholar
• Alegre E, López AS, González A. Tryptophan metabolites interfere with the Ehrlich reaction used for the measurement of kynurenine. Anal Biochem. 2005;339:188–189.
   PubMed Web of Science ®Google Scholar
• Sono M, Cady SG. Enzyme kinetic and spectroscopic studies of inhibitor and effector interactions with indoleamine 2,3-dioxygenase. 1. Norharman and 4-phenylimidazole binding to the enzyme as inhibitors and heme ligands. Biochemistry. 1989;28:5392–5399.
   PubMed Web of Science ®Google Scholar
• Kumar S, Jaller D, Patel B, et al. Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase. J Med Chem. 2008;51:4968–4977.
   PubMed Web of Science ®Google Scholar
• IOmet Pharma Ltd. Pharmaceutical compound. WO2016026772. 2016.
   Google Scholar
• Newlink Genetics Corp. Fused imidazole derivatives useful as IDO inhibitors. WO2012142237. 2012.
   Google Scholar
• Newlink Genetics Corp. Tricyclic compounds as inhibitors of immunosuppression mediated by tryptophan metabolization. WO2014159248. 2014.
   Google Scholar
• Hangzhou Innogate Pharma Co Ltd. Heterocycles useful as IDO and TDO inhibitors. WO2016165613. 2016.
   Google Scholar
• RedX Pharma Plc. 4H-imidazo[1,5-a]indole derivatives and their use as indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO2) modulators. WO2016051181. 2016.
   Google Scholar
• RedX Pharma Plc. 6,7-heterocyclic fused 5H-pyrrolo[1,2-c]imidazole derivatives and their use as indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO2) modulators. WO2016059412. 2016.
   Google Scholar
• Genentech Inc. TDO2 inhibitors. WO2017107979. 2017.
   Google Scholar
• Shanghai De Novo Pharmatech Co Ltd. Fused-ring compounds, pharmaceutical composition and uses thereof. WO2016131381. 2016.
   Google Scholar
• Shanghai Institute of organic chemistry. Indoleamine-2,3-dioxygenase inhibitor and preparation method thereof. WO2018082567. 2018.
   Google Scholar
• SciFluor Life Sciences Inc. Fused imidazole derivatives as IDO/TDO inhibitors. US20170121325. 2017.
   Google Scholar
• Emcure. Heterocyclic compounds useful as IDO and/or TDO modulators. WO2017149469. 2017.
   Google Scholar
• Curadev Pharma. Inhibitors of the kynurenine pathway. WO2014186035. 2014.
   Google Scholar
• iTEOS Therapeutics. 4-(indol-3-yl)-pyrazole derivatives, pharmaceutical compositions and methods for use. WO2015067782. 2015.
   Google Scholar
• iTEOS Therapeutics. Novel 3-(indol-3-yl)-pyridine derivatives, pharmaceutical compositions and methods for use. US2015225367. 2015.
   Google Scholar
• iTEOS Therapeutics. Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use. WO2015140717. 2015.
   Google Scholar
• iTEOS Therapeutics. Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use. US2018222862. 2018.
   Google Scholar
• Netherlands Translational Research Center. Inhibitors of tryptophan 2,3-dioxygenase. WO2018011227. 2018.
   Google Scholar
• IOmet Pharma Ltd. Pharmaceutical compound. WO2015082499. 2015.
   Google Scholar
• IOmet Pharma Ltd. Indole derivatives for use in medicine. WO2015150097. 2015.
   Google Scholar
• IOmet Pharma Ltd. Inhibitors of tryptophan 2,3-dioxygenase or indoleamine 2,3-dioxygenase WO2016071283. 2016.
   Google Scholar
• BeiGene Ltd. Novel 5 or 8-substituted imidazo[1, 5-a] pyridines as indoleamine and/or tryptophan 2,3-dioxygenase inhibitors. US20180072716. 2018.
   Google Scholar
• Auckland Uniservices Ltd. Inhibitors of tryptophan dioxygenases (IDO1 and TDO) and their use in therapy. WO2016024233. 2016.
   Google Scholar
• Auckland Uniservices Ltd. Inhibitors of tryptophan dioxygenases (IDO1 and TDO) and their use in therapy. WO2017034420. 2017.
   Google Scholar
• Beatty GL, O’Dwyer PJ, Clark J, et al. First-in-human phase I study of the oral inhibitor of indoleamine 2,3-dioxygenase-1 epacadostat (INCB024360) in patients with advanced solid malignancies. Clin Cancer Res. 2017;23:3269–3276.
   Web of Science ®Google Scholar