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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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General Review Article

Targeting TYK2 for Fighting Diseases: Recent Advance of TYK2 Inhibitors

Author(s): Si-Shi Du, Yu-Qing Fang, Wen Zhang and Guo-Wu Rao*

Volume 31, Issue 20, 2024

Published on: 21 June, 2023

Page: [2900 - 2920] Pages: 21

DOI: 10.2174/0929867330666230324163414

Price: $65

Abstract

TYK2 (tyrosine-protein kinase 2) is a non-receptor protein kinase belonging to the JAK family and is closely associated with various diseases, such as psoriasis, inflammatory bowel disease, systemic lupus erythematosus. TYK2 activates the downstream proteins STAT1-5 by participating in the signal transduction of immune factors such as IL-12, IL-23, and IL-10, resulting in immune expression. The activity of the inhibitor TYK2 can effectively block the transduction of excessive immune signals and treat diseases. TYK2 inhibitors are divided into two types of inhibitors according to the different binding sites. One is a TYK2 inhibitor that binds to JH2 and inhibits its activity through an allosteric mechanism. The representative inhibitor is BMS-986165, developed by Bristol-Myers Squibb. The other class binds to the JH1 adenosine triphosphate (ATP) site and prevents the catalytic activity of the kinase by blocking ATP and downstream phosphorylation. This paper mainly introduces the protein structure, signaling pathway, synthesis, structure-activity relationship and clinical research of TYK2 inhibitors.

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[1]
Ciechanowicz, P.; Rakowska, A.; Sikora, M.; Rudnicka, L. JAK-inhibitors in dermatology: current evidence and future applications. J. Dermatolog. Treat., 2019, 30(7), 648-658.
[http://dx.doi.org/10.1080/09546634.2018.1546043] [PMID: 30433838]
[2]
Serra López-Matencio, J.M.; Morell Baladrón, A.; Castañeda, S. JAK-STAT inhibitors for the treatment of immunomediated diseases. Med. Clin., 2019, 152(9), 353-360.
[PMID: 30527218]
[3]
Xu, P.; Shen, P.; Yu, B.; Xu, X.; Ge, R.; Cheng, X.; Chen, Q.; Bian, J.; Li, Z.; Wang, J. Janus kinases (JAKs): The efficient therapeutic targets for autoimmune diseases and myeloproliferative disorders. Eur. J. Med. Chem., 2020, 192, 112155.
[http://dx.doi.org/10.1016/j.ejmech.2020.112155] [PMID: 32120325]
[4]
Shaw, M.H.; Boyartchuk, V.; Wong, S.; Karaghiosoff, M.; Ragimbeau, J.; Pellegrini, S.; Muller, M.; Dietrich, W.F.; Yap, G.S. A natural mutation in the Tyk2 pseudokinase domain underlies altered susceptibility of B10.Q/J mice to infection and autoimmunity. Proc. Natl. Acad. Sci. USA, 2003, 100(20), 11594-11599.
[http://dx.doi.org/10.1073/pnas.1930781100] [PMID: 14500783]
[5]
Sobhkhez, M.; Hansen, T.; Iliev, D.B.; Skjesol, A.; Jørgensen, J.B. The Atlantic salmon protein tyrosine kinase Tyk2: Molecular cloning, modulation of expression and function. Dev. Comp. Immunol., 2013, 41(4), 553-563.
[http://dx.doi.org/10.1016/j.dci.2013.07.008] [PMID: 23872231]
[6]
Roskoski, R.Jr. Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases. Pharmacol. Res., 2016, 111, 784-803.
[http://dx.doi.org/10.1016/j.phrs.2016.07.038] [PMID: 27473820]
[7]
Saharinen, P.; Vihinen, M.; Silvennoinen, O. Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain. Mol. Biol. Cell, 2003, 14(4), 1448-1459.
[http://dx.doi.org/10.1091/mbc.e02-06-0342] [PMID: 12686600]
[8]
Min, X.; Ungureanu, D.; Maxwell, S.; Hammarén, H.; Thibault, S.; Hillert, E.K.; Ayres, M.; Greenfield, B.; Eksterowicz, J.; Gabel, C.; Walker, N.; Silvennoinen, O.; Wang, Z. Structural and functional characterization of the JH2 pseudokinase domain of JAK Family Tyrosine Kinase 2 (TYK2). J. Biol. Chem., 2015, 290(45), 27261-27270.
[http://dx.doi.org/10.1074/jbc.M115.672048] [PMID: 26359499]
[9]
Ferrao, R.; Lupardus, P.J. The janus kinase (JAK) FERM and SH2 domains: Bringing specificity to JAK–receptor interactions. Front. Endocrinol., 2017, 8, 71.
[http://dx.doi.org/10.3389/fendo.2017.00071] [PMID: 28458652]
[10]
Lupardus, P.J.; Ultsch, M.; Wallweber, H.; Bir Kohli, P.; Johnson, A.R.; Eigenbrot, C. Structure of the pseudokinase–kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition. Proc. Natl. Acad. Sci. USA, 2014, 111(22), 8025-8030.
[http://dx.doi.org/10.1073/pnas.1401180111] [PMID: 24843152]
[11]
Strobl, B.; Stoiber, D.; Sexl, V.; Mueller, M. Tyrosine kinase 2 (TYK2) in cytokine signalling and host immunity. Front. Biosci., 2011, 16(9), 3214-3232.
[PMID: 21622231]
[12]
Raivola, J.; Haikarainen, T.; Silvennoinen, O. Characterization of JAK1 pseudokinase domain in cytokine signaling. Cancers, 2019, 12(1), 78.
[http://dx.doi.org/10.3390/cancers12010078] [PMID: 31892268]
[13]
Silvennoinen, O.; Ungureanu, D.; Niranjan, Y.; Hammaren, H.; Bandaranayake, R.; Hubbard, S.R. New insights into the structure and function of the pseudokinase domain in JAK2. Biochem. Soc. Trans., 2013, 41(4), 1002-1007.
[http://dx.doi.org/10.1042/BST20130005] [PMID: 23863170]
[14]
Hadjadj, J.; Frémond, M.L.; Neven, B. Emerging Place of JAK inhibitors in the treatment of inborn errors of immunity. Front. Immunol., 2021, 12, 717388.
[http://dx.doi.org/10.3389/fimmu.2021.717388] [PMID: 34603291]
[15]
De Smedt, R.; Morscio, J.; Goossens, S.; Van Vlierberghe, P. Targeting steroid resistance in T-cell acute lymphoblastic leukemia. Blood Rev., 2019, 38, 100591.
[http://dx.doi.org/10.1016/j.blre.2019.100591] [PMID: 31353059]
[16]
Hin Tang, J.J.; Hao Thng, D.K.; Lim, J.J.; Toh, T.B. JAK/STAT signaling in hepatocellular carcinoma. Hepat. Oncol., 2020, 7(1), HEP18.
[http://dx.doi.org/10.2217/hep-2020-0001] [PMID: 32273976]
[17]
Mohanty, S.K.; Yagiz, K.; Pradhan, D.; Luthringer, D.J.; Amin, M.B.; Alkan, S.; Cinar, B. STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer. Oncotarget, 2017, 8(49), 85997-86010.
[http://dx.doi.org/10.18632/oncotarget.20844] [PMID: 29156772]
[18]
Ruan, Z.; Yang, X.; Cheng, W. OCT4 accelerates tumorigenesis through activating JAK/STAT signaling in ovarian cancer side population cells. Cancer Manag. Res., 2018, 11, 389-399.
[http://dx.doi.org/10.2147/CMAR.S180418] [PMID: 30643464]
[19]
Mascareno, E.; Siddiqui, M.A.Q. The role of Jak/STAT signaling in heart tissue renin-angiotensin system. Mol. Cell. Biochem., 2000, 212(1/2), 171-175.
[http://dx.doi.org/10.1023/A:1007157126806] [PMID: 11108148]
[20]
Booz, G.W.; Day, J.N.E.; Baker, K.M. Interplay between the cardiac renin angiotensin system and JAK-STAT signaling: role in cardiac hypertrophy, ischemia/reperfusion dysfunction, and heart failure. J. Mol. Cell. Cardiol., 2002, 34(11), 1443-1453.
[http://dx.doi.org/10.1006/jmcc.2002.2076] [PMID: 12431443]
[21]
García-Melendo, C.; Cubiró, X.; Puig, L. Janus kinase inhibitors in dermatology: Part 2: Applications in psoriasis, atopic dermatitis, and other dermatoses. Actas. Dermosifiliogr (Engl Ed)., 2021, S0001-7310(21), 00006-5.
[22]
Wang, L.; Hu, Y.; Song, B.; Xiong, Y.; Wang, J.; Chen, D. Targeting JAK/STAT signaling pathways in treatment of inflammatory bowel disease. Inflamm. Res., 2021, 70(7), 753-764.
[http://dx.doi.org/10.1007/s00011-021-01482-x] [PMID: 34212215]
[23]
Sperti, M.; Malavolta, M.; Ciniero, G.; Borrelli, S.; Cavaglià, M.; Muscat, S.; Tuszynski, J.A.; Afeltra, A.; Margiotta, D.P.E.; Navarini, L. JAK inhibitors in immune-mediated rheumatic diseases: From a molecular perspective to clinical studies. J. Mol. Graph. Model., 2021, 104, 107789.
[http://dx.doi.org/10.1016/j.jmgm.2020.107789] [PMID: 33472140]
[24]
Babon, J.J.; Lucet, I.S.; Murphy, J.M.; Nicola, N.A.; Varghese, L.N. The molecular regulation of Janus kinase (JAK) activation. Biochem. J., 2014, 462(1), 1-13.
[http://dx.doi.org/10.1042/BJ20140712] [PMID: 25057888]
[25]
Shuai, K.; Schindler, C.; Prezioso, V.R.; Darnell, J.E., Jr Activation of transcription by IFN-gamma: Tyrosine phosphorylation of a 91-kD DNA binding protein. Science, 1992, 258(5089), 1808-1812.
[http://dx.doi.org/10.1126/science.1281555] [PMID: 1281555]
[26]
Mitchell, T.J.; John, S. Signal transducer and activator of transcription (STAT) signalling and T-cell lymphomas. Immunology, 2005, 114(3), 301-312.
[http://dx.doi.org/10.1111/j.1365-2567.2005.02091.x] [PMID: 15720432]
[27]
Ivashkiv, L.B.; Donlin, L.T. Regulation of type I interferon responses. Nat. Rev. Immunol., 2014, 14(1), 36-49.
[http://dx.doi.org/10.1038/nri3581] [PMID: 24362405]
[28]
Li, S.; Gong, M.; Zhao, F.; Shao, J.; Xie, Y.; Zhang, Y.; Chang, H.; Type, I. Type I Interferons: Distinct biological activities and current applications for viral infection. Cell. Physiol. Biochem., 2018, 51(5), 2377-2396.
[http://dx.doi.org/10.1159/000495897] [PMID: 30537741]
[29]
Gallucci, S.; Meka, S.; Gamero, A.M. Abnormalities of the type I interferon signaling pathway in lupus autoimmunity. Cytokine, 2021, 146, 155633.
[http://dx.doi.org/10.1016/j.cyto.2021.155633] [PMID: 34340046]
[30]
Karjalainen, A.; Shoebridge, S.; Krunic, M.; Simonović, N.; Tebb, G.; Macho-Maschler, S.; Strobl, B.; Müller, M. TYK2 in tumor immunosurveillance. Cancers, 2020, 12(1), 150.
[http://dx.doi.org/10.3390/cancers12010150] [PMID: 31936322]
[31]
Uzé, G.; Schreiber, G.; Piehler, J.; Pellegrini, S. The receptor of the type I interferon family. Curr. Top. Microbiol. Immunol., 2007, 316, 71-95.
[http://dx.doi.org/10.1007/978-3-540-71329-6_5] [PMID: 17969444]
[32]
Gauzzi, M.C.; Barbieri, G.; Richter, M.F.; Uzé, G.; Ling, L.; Fellous, M.; Pellegrini, S. The amino-terminal region of Tyk2 sustains the level of interferon α receptor 1, a component of the interferon α/β receptor. Proc. Natl. Acad. Sci. USA, 1997, 94(22), 11839-11844.
[http://dx.doi.org/10.1073/pnas.94.22.11839] [PMID: 9342324]
[33]
Ragimbeau, J.; Dondi, E.; Alcover, A.; Eid, P.; Uzé, G.; Pellegrini, S. The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. EMBO J., 2003, 22(3), 537-547.
[http://dx.doi.org/10.1093/emboj/cdg038] [PMID: 12554654]
[34]
Shimoda, K.; Kato, K.; Aoki, K.; Matsuda, T.; Miyamoto, A.; Shibamori, M.; Yamashita, M.; Numata, A.; Takase, K.; Kobayashi, S.; Shibata, S.; Asano, Y.; Gondo, H.; Sekiguchi, K.; Nakayama, K.; Nakayama, T.; Okamura, T.; Okamura, S.; Niho, Y.; Nakayama, K. Tyk2 plays a restricted role in IFN-alpha signaling, although it is required for IL-12-mediated T cell function. Immunity, 2000, 13(4), 561-571.
[http://dx.doi.org/10.1016/S1074-7613(00)00055-8] [PMID: 11070174]
[35]
Rani, M.R.S.; Gauzzi, C.; Pellegrini, S.; Fish, E.N.; Wei, T.; Ransohoff, R.M. Induction of beta-R1/I-TAC by interferon-beta requires catalytically active TYK2. J. Biol. Chem., 1999, 274(4), 1891-1897.
[http://dx.doi.org/10.1074/jbc.274.4.1891] [PMID: 9890942]
[36]
Rani, M.R.S.; Pandalai, S.; Shrock, J.; Almasan, A.; Ransohoff, R.M. Requirement of catalytically active Tyk2 and accessory signals for the induction of TRAIL mRNA by IFN-beta. J. Interferon Cytokine Res., 2007, 27(9), 767-780.
[http://dx.doi.org/10.1089/jir.2007.0005] [PMID: 17892398]
[37]
Thompson, A.; Orr, S.J. Emerging IL-12 family cytokines in the fight against fungal infections. Cytokine, 2018, 111, 398-407.
[http://dx.doi.org/10.1016/j.cyto.2018.05.019] [PMID: 29793796]
[38]
Zelante, T.; Bozza, S.; De, L.A.; D'Angelo, C.; Bonifazi, P.; Moretti, S.; Giovannini, G.; Bistoni, F.; Romani, L. Th17 cells in the setting of Aspergillus infection and pathology. Med Mycol., 2009, 47(Suppl 1), S162-9.
[39]
Haines, C.J.; Chen, Y.; Blumenschein, W.M.; Jain, R.; Chang, C.; Joyce-Shaikh, B.; Porth, K.; Boniface, K.; Mattson, J.; Basham, B.; Anderton, S.M.; McClanahan, T.K.; Sadekova, S.; Cua, D.J.; McGeachy, M.J. Autoimmune memory T helper 17 cell function and expansion are dependent on interleukin-23. Cell Rep., 2013, 3(5), 1378-1388.
[http://dx.doi.org/10.1016/j.celrep.2013.03.035] [PMID: 23623497]
[40]
Lucas, S.; Ghilardi, N.; Li, J.; de Sauvage, F.J. IL-27 regulates IL-12 responsiveness of naïve CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc. Natl. Acad. Sci. USA, 2003, 100(25), 15047-15052.
[http://dx.doi.org/10.1073/pnas.2536517100] [PMID: 14657353]
[41]
Pflanz, S.; Timans, J.C.; Cheung, J.; Rosales, R.; Kanzler, H.; Gilbert, J.; Hibbert, L.; Churakova, T.; Travis, M.; Vaisberg, E.; Blumenschein, W.M.; Mattson, J.D.; Wagner, J.L.; To, W.; Zurawski, S.; McClanahan, T.K.; Gorman, D.M.; Bazan, J.F.; de Waal Malefyt, R.; Rennick, D.; Kastelein, R.A. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity, 2002, 16(6), 779-790.
[http://dx.doi.org/10.1016/S1074-7613(02)00324-2] [PMID: 12121660]
[42]
Chyuan, I.T.; Lai, J.H. New insights into the IL-12 and IL-23: From a molecular basis to clinical application in immune-mediated inflammation and cancers. Biochem. Pharmacol., 2020, 175, 113928.
[http://dx.doi.org/10.1016/j.bcp.2020.113928] [PMID: 32217101]
[43]
Floss, D.M.; Klöcker, T.; Schröder, J.; Lamertz, L.; Mrotzek, S.; Strobl, B.; Hermanns, H.; Scheller, J. Defining the functional binding sites of interleukin 12 receptor β1 and interleukin 23 receptor to Janus kinases. Mol. Biol. Cell, 2016, 27(14), 2301-2316.
[http://dx.doi.org/10.1091/mbc.E14-12-1645] [PMID: 27193299]
[44]
Liberman, A.C.; Refojo, D.; Arzt, E. Cytokine signaling/transcription factor cross-talk in T cell activation and Th1-Th2 differentiation. Arch. Immunol. Ther. Exp., 2003, 51(6), 351-365.
[PMID: 14692657]
[45]
Lederer, J.A.; Perez, V.L.; DesRoches, L.; Kim, S.M.; Abbas, A.K.; Lichtman, A.H. Cytokine transcriptional events during helper T cell subset differentiation. J. Exp. Med., 1996, 184(2), 397-406.
[http://dx.doi.org/10.1084/jem.184.2.397] [PMID: 8760793]
[46]
Liu, J.; Cao, S.; Kim, S.; Chung, E.; Homma, Y.; Guan, X.; Jimenez, V.; Ma, X. Interleukin-12: an update on its immunological activities, signaling and regulation of gene expression. Curr. Immunol. Rev., 2005, 1(2), 119-137.
[http://dx.doi.org/10.2174/1573395054065115] [PMID: 21037949]
[47]
Vignali, D.A.A.; Kuchroo, V.K. IL-12 family cytokines: Immunological playmakers. Nat. Immunol., 2012, 13(8), 722-728.
[http://dx.doi.org/10.1038/ni.2366] [PMID: 22814351]
[48]
Chang, J.T.; Segal, B.M.; Nakanishi, K.; Okamura, H.; Shevach, E.M. The costimulatory effect of IL-18 on the induction of antigen-specific IFN-γ production by resting T cells is IL-12 dependent and is mediated by up-regulation of the IL-12 receptor β2 subunit. Eur. J. Immunol., 2000, 30(4), 1113-1119.
[http://dx.doi.org/10.1002/(SICI)1521-4141(200004)30:4<1113::AID-IMMU1113>3.0.CO;2-P] [PMID: 10760800]
[49]
Ishizaki, M.; Muromoto, R.; Akimoto, T.; Sekine, Y.; Kon, S.; Diwan, M.; Maeda, H.; Togi, S.; Shimoda, K.; Oritani, K.; Matsuda, T. Tyk2 is a therapeutic target for psoriasis-like skin inflammation. Int. Immunol., 2014, 26(5), 257-267.
[http://dx.doi.org/10.1093/intimm/dxt062] [PMID: 24345760]
[50]
Simon, L.S.; Taylor, P.C.; Choy, E.H.; Sebba, A.; Quebe, A.; Knopp, K.L.; Porreca, F. The Jak/STAT pathway: A focus on pain in rheumatoid arthritis. Semin. Arthritis Rheum., 2021, 51(1), 278-284.
[http://dx.doi.org/10.1016/j.semarthrit.2020.10.008] [PMID: 33412435]
[51]
Muromoto, R.; Shimoda, K.; Oritani, K.; Matsuda, T. Therapeutic advantage of Tyk2 inhibition for treating autoimmune and chronic inflammatory diseases. Biol. Pharm. Bull., 2021, 44(11), 1585-1592.
[http://dx.doi.org/10.1248/bpb.b21-00609] [PMID: 34719635]
[52]
Mannino, M.H.; Zhu, Z.; Xiao, H.; Bai, Q.; Wakefield, M.R.; Fang, Y. The paradoxical role of IL-10 in immunity and cancer. Cancer Lett., 2015, 367(2), 103-107.
[http://dx.doi.org/10.1016/j.canlet.2015.07.009] [PMID: 26188281]
[53]
Übel, C.; Mousset, S.; Trufa, D.; Sirbu, H.; Finotto, S. Establishing the role of tyrosine kinase 2 in cancer. OncoImmunology, 2013, 2(1), e22840.
[http://dx.doi.org/10.4161/onci.22840] [PMID: 23482926]
[54]
Prchal-Murphy, M.; Witalisz-Siepracka, A.; Bednarik, K.T.; Putz, E.M.; Gotthardt, D.; Meissl, K.; Sexl, V.; Müller, M.; Strobl, B. In vivo tumor surveillance by NK cells requires TYK2 but not TYK2 kinase activity. OncoImmunology, 2015, 4(11), e1047579.
[http://dx.doi.org/10.1080/2162402X.2015.1047579] [PMID: 26451322]
[55]
Qin, W.; Godec, A.; Zhang, X.; Zhu, C.; Shao, J.; Tao, Y.; Bu, X.; Hirbe, A.C. TYK2 promotes malignant peripheral nerve sheath tumor progression through inhibition of cell death. Cancer Med., 2019, 8(11), 5232-5241.
[http://dx.doi.org/10.1002/cam4.2386] [PMID: 31278855]
[56]
Wöss, K.; Simonović, N.; Strobl, B.; Macho-Maschler, S.; Müller, M. TYK2: An upstream kinase of STATs in cancer. Cancers (Basel), 2019, 11(11), 1728.
[http://dx.doi.org/10.3390/cancers11111728] [PMID: 31694222]
[57]
Silver, D.L.; Naora, H.; Liu, J.; Cheng, W.; Montell, D.J. Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility. Cancer Res., 2004, 64(10), 3550-3558.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3959] [PMID: 15150111]
[58]
Song, X.C.; Fu, G.; Yang, X.; Jiang, Z.; Wang, Y.; Zhou, G.W. Protein expression profiling of breast cancer cells by dissociable antibody microarray (DAMA) staining. Mol. Cell. Proteomics, 2008, 7(1), 163-169.
[http://dx.doi.org/10.1074/mcp.M700115-MCP200] [PMID: 17934210]
[59]
Lowes, M.A.; Bowcock, A.M.; Krueger, J.G. Pathogenesis and therapy of psoriasis. Nature, 2007, 445(7130), 866-873.
[http://dx.doi.org/10.1038/nature05663] [PMID: 17314973]
[60]
van der Fits, L.; Mourits, S.; Voerman, J.S.A.; Kant, M.; Boon, L.; Laman, J.D.; Cornelissen, F.; Mus, A.M.; Florencia, E.; Prens, E.P.; Lubberts, E. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J. Immunol., 2009, 182(9), 5836-5845.
[http://dx.doi.org/10.4049/jimmunol.0802999] [PMID: 19380832]
[61]
Balogh, E.A.; Bashyam, A.M.; Ghamrawi, R.I.; Feldman, S.R. Emerging systemic drugs in the treatment of plaque psoriasis. Expert Opin. Emerg. Drugs, 2020, 25(2), 89-100.
[http://dx.doi.org/10.1080/14728214.2020.1745773] [PMID: 32192366]
[62]
Liu, S.; Ma, H.; Zhang, H.; Deng, C.; Xin, P. Recent advances on signaling pathways and their inhibitors in rheumatoid arthritis. Clin. Immunol., 2021, 230, 108793.
[http://dx.doi.org/10.1016/j.clim.2021.108793] [PMID: 34242749]
[63]
Peng, Y.; Chen, B.; Sheng, X.; Qian, Y. Polymorphisms in IRF5 and TYK2 genes are associated with rheumatoid arthritis in a Chinese Han population. Med. Sci. Monit., 2021, 27, e928455.
[http://dx.doi.org/10.12659/MSM.928455] [PMID: 33583939]
[64]
Diogo, D.; Bastarache, L.; Liao, K.P.; Graham, R.R.; Fulton, R.S.; Greenberg, J.D.; Eyre, S.; Bowes, J.; Cui, J.; Lee, A.; Pappas, D.A.; Kremer, J.M.; Barton, A.; Coenen, M.J.H.; Franke, B.; Kiemeney, L.A.; Mariette, X.; Richard-Miceli, C.; Canhão, H.; Fonseca, J.E.; de Vries, N.; Tak, P.P.; Crusius, J.B.A.; Nurmohamed, M.T.; Kurreeman, F.; Mikuls, T.R.; Okada, Y.; Stahl, E.A.; Larson, D.E.; Deluca, T.L.; O’Laughlin, M.; Fronick, C.C.; Fulton, L.L.; Kosoy, R.; Ransom, M.; Bhangale, T.R.; Ortmann, W.; Cagan, A.; Gainer, V.; Karlson, E.W.; Kohane, I.; Murphy, S.N.; Martin, J.; Zhernakova, A.; Klareskog, L.; Padyukov, L.; Worthington, J.; Mardis, E.R.; Seldin, M.F.; Gregersen, P.K.; Behrens, T.; Raychaudhuri, S.; Denny, J.C.; Plenge, R.M. TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits. PLoS One, 2015, 10(4), e0122271.
[http://dx.doi.org/10.1371/journal.pone.0122271] [PMID: 25849893]
[65]
Faust, A.H.; Halpern, L.F.; Danoff-Burg, S.; Cross, R.K. Psychosocial factors contributing to inflammatory bowel disease activity and health-related quality of life. Gastroenterol. Hepatol., 2012, 8(3), 173-181.
[PMID: 22675279]
[66]
de Souza, H.S.P.; Fiocchi, C. Immunopathogenesis of IBD: current state of the art. Nat. Rev. Gastroenterol. Hepatol., 2016, 13(1), 13-27.
[http://dx.doi.org/10.1038/nrgastro.2015.186] [PMID: 26627550]
[67]
Roda, G.; Dal Buono, A.; Argollo, M.; Danese, S. JAK selectivity: More precision less troubles. Expert Rev. Gastroenterol. Hepatol., 2020, 14(9), 789-796.
[http://dx.doi.org/10.1080/17474124.2020.1780120] [PMID: 32520647]
[68]
Danese, S.; Argollo, M.; Le Berre, C.; Peyrin-Biroulet, L. JAK selectivity for inflammatory bowel disease treatment: does it clinically matter? Gut, 2019, 68(10), 1893-1899.
[http://dx.doi.org/10.1136/gutjnl-2019-318448] [PMID: 31227590]
[69]
McKeon, K.P.; Jiang, S.H. Treatment of systemic lupus erythematosus. Aust. Prescr., 2020, 43(3), 85-90.
[http://dx.doi.org/10.18773/austprescr.2020.022] [PMID: 32675909]
[70]
Pawlak-Buś, K.; Schmidt, W.; Leszczyński, P. Lack of association between serum interleukin-23 and interleukin-27 levels and disease activity in patients with active systemic lupus erythematosus. J. Clin. Med., 2021, 10(20), 4788.
[http://dx.doi.org/10.3390/jcm10204788] [PMID: 34682911]
[71]
Bengtsson, A.A.; Sturfelt, G.; Truedsson, L.; Blomberg, J.; Alm, G.; Vallin, H.; Rönnblom, L. Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus, 2000, 9(9), 664-671.
[http://dx.doi.org/10.1191/096120300674499064] [PMID: 11199920]
[72]
Sigurdsson, S.; Nordmark, G.; Göring, H.H.H.; Lindroos, K.; Wiman, A.C.; Sturfelt, G.; Jönsen, A.; Rantapää-Dahlqvist, S.; Möller, B.; Kere, J.; Koskenmies, S.; Widén, E.; Eloranta, M.L.; Julkunen, H.; Kristjansdottir, H.; Steinsson, K.; Alm, G.; Rönnblom, L.; Syvänen, A.C. Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am. J. Hum. Genet., 2005, 76(3), 528-537.
[http://dx.doi.org/10.1086/428480] [PMID: 15657875]
[73]
Sharabi, A. Updates on clinical trials in systemic lupus erythematosus. Curr. Rheumatol. Rep., 2021, 23(7), 57.
[http://dx.doi.org/10.1007/s11926-021-01014-w] [PMID: 34212269]
[74]
Mallone, R.; Eizirik, D.L. Presumption of innocence for beta cells: Why are they vulnerable autoimmune targets in type 1 diabetes? Diabetologia, 2020, 63(10), 1999-2006.
[http://dx.doi.org/10.1007/s00125-020-05176-7] [PMID: 32894310]
[75]
Op de Beeck, A.; Eizirik, D.L. Viral infections in type 1 diabetes mellitus-why the β cells? Nat. Rev. Endocrinol., 2016, 12(5), 263-273.
[http://dx.doi.org/10.1038/nrendo.2016.30] [PMID: 27020257]
[76]
Marroqui, L.; Dos Santos, R.S.; Fløyel, T.; Grieco, F.A.; Santin, I.; Op de beeck, A.; Marselli, L.; Marchetti, P.; Pociot, F.; Eizirik, D.L. TYK2, a candidate gene for type 1 diabetes, modulates apoptosis and the innate immune response in human pancreatic β-cells. Diabetes, 2015, 64(11), 3808-3817.
[http://dx.doi.org/10.2337/db15-0362] [PMID: 26239055]
[77]
Toms, A.V.; Deshpande, A.; McNally, R.; Jeong, Y.; Rogers, J.M.; Kim, C.U.; Gruner, S.M.; Ficarro, S.B.; Marto, J.A.; Sattler, M.; Griffin, J.D.; Eck, M.J. Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases. Nat. Struct. Mol. Biol., 2013, 20(10), 1221-1223.
[http://dx.doi.org/10.1038/nsmb.2673] [PMID: 24013208]
[78]
Saharinen, P.; Silvennoinen, O. The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. J. Biol. Chem., 2002, 277(49), 47954-47963.
[http://dx.doi.org/10.1074/jbc.M205156200] [PMID: 12351625]
[79]
Tokarski, J.S.; Zupa-Fernandez, A.; Tredup, J.A.; Pike, K.; Chang, C.; Xie, D.; Cheng, L.; Pedicord, D.; Muckelbauer, J.; Johnson, S.R.; Wu, S.; Edavettal, S.C.; Hong, Y.; Witmer, M.R.; Elkin, L.L.; Blat, Y.; Pitts, W.J.; Weinstein, D.S.; Burke, J.R. Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes is blocked by pharmacological stabilization of its pseudokinase domain. J. Biol. Chem., 2015, 290(17), 11061-11074.
[http://dx.doi.org/10.1074/jbc.M114.619502] [PMID: 25762719]
[80]
Burke, J.R.; Cheng, L.; Gillooly, K.M.; Strnad, J.; Zupa-Fernandez, A.; Catlett, I.M.; Zhang, Y.; Heimrich, E.M.; McIntyre, K.W.; Cunningham, M.D.; Carman, J.A.; Zhou, X.; Banas, D.; Chaudhry, C.; Li, S.; D'Arienzo, C.; Chimalakonda, A.; Yang, X.; Xie, J.H.; Pang, J.; Zhao, Q.; Rose, S.M.; Huang, J.; Moslin, R.M.; Wrobleski, S.T.; Weinstein, D.S.; Salter-Cid, L.M. Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci. Transl. Med., 2019, 11(502), eaaw1736.
[http://dx.doi.org/10.1126/scitranslmed.aaw1736]
[81]
Nogueira, M.; Puig, L.; Torres, T. JAK inhibitors for treatment of psoriasis: Focus on selective TYK2 inhibitors. Drugs, 2020, 80(4), 341-352.
[http://dx.doi.org/10.1007/s40265-020-01261-8] [PMID: 32020553]
[82]
Wrobleski, S.T.; Moslin, R.; Lin, S.; Zhang, Y.; Spergel, S.; Kempson, J.; Tokarski, J.S.; Strnad, J.; Zupa-Fernandez, A.; Cheng, L.; Shuster, D.; Gillooly, K.; Yang, X.; Heimrich, E.; McIntyre, K.W.; Chaudhry, C.; Khan, J.; Ruzanov, M.; Tredup, J.; Mulligan, D.; Xie, D.; Sun, H.; Huang, C.; D’Arienzo, C.; Aranibar, N.; Chiney, M.; Chimalakonda, A.; Pitts, W.J.; Lombardo, L.; Carter, P.H.; Burke, J.R.; Weinstein, D.S. Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the treatment of autoimmune diseases: discovery of the allosteric inhibitor BMS-986165. J. Med. Chem., 2019, 62(20), 8973-8995.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00444] [PMID: 31318208]
[83]
Catlett, I.; Aras, U.; Liu, Y.; Bei, D.; Girgis, I.; Murthy, B.; Hon-czarenko, M.; Rose, S. ln: Rheumatology Proceedings of the Annual European Congress of Rheumatology, Madrid, Spain. June 14-17,2017, p. 859.
[84]
Papp, K.; Gordon, K.; Thaçi, D.; Morita, A.; Gooderham, M.; Foley, P.; Girgis, I.G.; Kundu, S.; Banerjee, S. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N. Engl. J. Med., 2018, 379(14), 1313-1321.
[http://dx.doi.org/10.1056/NEJMoa1806382] [PMID: 30205746]
[85]
Jiang, L.; Li, Z.; Rui, L. Leptin stimulates both JAK2-dependent and JAK2-independent signaling pathways. J. Biol. Chem., 2008, 283(42), 28066-28073.
[http://dx.doi.org/10.1074/jbc.M805545200] [PMID: 18718905]
[86]
Liu, C.; Lin, J.; Langevine, C.; Smith, D.; Li, J.; Tokarski, J.S.; Khan, J.; Ruzanov, M.; Strnad, J.; Zupa-Fernandez, A.; Cheng, L.; Gillooly, K.M.; Shuster, D.; Zhang, Y.; Thankappan, A.; McIntyre, K.W.; Chaudhry, C.; Elzinga, P.A.; Chiney, M.; Chimalakonda, A.; Lombardo, L.J.; Macor, J.E.; Carter, P.H.; Burke, J.R.; Weinstein, D.S. Discovery of BMS-986202: A Clinical Tyk2 inhibitor that binds to Tyk2 JH2. J. Med. Chem., 2021, 64(1), 677-694.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01698] [PMID: 33370104]
[87]
Nash, O.; Omotuyi, O.; Lee, J.; Kwon, B.M.; Ogbadu, L. Artocarpus altilis CG-901 alters critical nodes in the JH1-kinase domain of Janus kinase 2 affecting upstream JAK/STAT3 signaling. J. Mol. Model., 2015, 21(11), 280.
[http://dx.doi.org/10.1007/s00894-015-2821-z] [PMID: 26442513]
[88]
Gu, J.; Wang, Y.; Gu, X. Evolutionary analysis for functional divergence of Jak protein kinase domains and tissue-specific genes. J. Mol. Evol., 2002, 54(6), 725-733.
[http://dx.doi.org/10.1007/s00239-001-0072-3] [PMID: 12029354]
[89]
Page, K.M.; Suarez-Farinas, M.; Suprun, M.; Zhang, W.; Garcet, S.; Fuentes-Duculan, J.; Li, X.; Scaramozza, M.; Kieras, E.; Banfield, C.; Clark, J.D.; Fensome, A.; Krueger, J.G.; Peeva, E. Molecular and cellular responses to the TYK2/JAK1 inhibitor PF-06700841 reveal reduction of skin inflammation in plaque psoriasis. J. Invest. Dermatol., 2020, 140(8), 1546-1555.e4.
[http://dx.doi.org/10.1016/j.jid.2019.11.027] [PMID: 31972249]
[90]
Tehlirian, C.; Singh, R.S.P.; Pradhan, V.; Roberts, E.S.; Tarabar, S.; Peeva, E.; Vincent, M.S.; Gale, J.D. Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study. J. Am. Acad. Dermatol., 2022, S0190-9622(22), 00552-7.
[91]
Fensome, A.; Ambler, C.M.; Arnold, E.; Banker, M.E.; Brown, M.F.; Chrencik, J.; Clark, J.D.; Dowty, M.E.; Efremov, I.V.; Flick, A.; Gerstenberger, B.S.; Gopalsamy, A.; Hayward, M.M.; Hegen, M.; Hollingshead, B.D.; Jussif, J.; Knafels, J.D.; Limburg, D.C.; Lin, D.; Lin, T.H.; Pierce, B.S.; Saiah, E.; Sharma, R.; Symanowicz, P.T.; Telliez, J.B.; Trujillo, J.I.; Vajdos, F.F.; Vincent, F.; Wan, Z.K.; Xing, L.; Yang, X.; Yang, X.; Zhang, L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S )-2,2-Difluorocyclopropyl)((1 R, 5 S )-3-(2-((1-methyl-1 H -pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J. Med. Chem., 2018, 61(19), 8597-8612.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00917] [PMID: 30113844]
[92]
Banfield, C.; Scaramozza, M.; Zhang, W.; Kieras, E.; Page, K.M.; Fensome, A.; Vincent, M.; Dowty, M.E.; Goteti, K.; Winkle, P.J.; Peeva, E. The safety, tolerability, pharmacokinetics, and pharmacodynamics of a TYK2/JAK1 inhibitor (PF-06700841) in healthy subjects and patients with plaque psoriasis. J. Clin. Pharmacol., 2018, 58(4), 434-447.
[http://dx.doi.org/10.1002/jcph.1046] [PMID: 29266308]
[93]
Forman, S.B.; Pariser, D.M.; Poulin, Y.; Vincent, M.S.; Gilbert, S.A.; Kieras, E.M.; Qiu, R.; Yu, D.; Papacharalambous, J.; Tehlirian, C.; Peeva, E. TYK2/JAK1 Inhibitor PF-06700841 in patients with plaque psoriasis: Phase IIa, randomized, double-blind, placebo-controlled trial. J. Invest. Dermatol., 2020, 140(12), 2359-2370.e5.
[http://dx.doi.org/10.1016/j.jid.2020.03.962] [PMID: 32311398]
[94]
Danese, S.; Peyrin-Biroulet, L. Selective tyrosine kinase 2 inhibition for treatment of inflammatory bowel disease: New hope on the rise. Inflamm. Bowel Dis., 2021, 27(12), 2023-2030.
[http://dx.doi.org/10.1093/ibd/izab135] [PMID: 34089259]
[95]
Jo, C.E.; Gooderham, M.; Beecker, J. TYK 2 inhibitors for the treatment of dermatologic conditions: The evolution of JAK inhibitors. Int. J. Dermatol., 2022, 61(2), 139-147.
[http://dx.doi.org/10.1111/ijd.15605] [PMID: 33929045]
[96]
Singh, R.S.P.; Pradhan, V.; Roberts, E.S.; Scaramozza, M.; Kieras, E.; Gale, J.D.; Peeva, E.; Vincent, M.S.; Banerjee, A.; Fensome, A.; Dowty, M.E.; Winkle, P.; Tehlirian, C. Safety and pharmacokinetics of the oral TYK2 inhibitor PF-06826647: A phase I, randomized, double-blind, placebo-controlled, dose-escalation study. Clin. Transl. Sci., 2021, 14(2), 671-682.
[http://dx.doi.org/10.1111/cts.12929] [PMID: 33290616]
[97]
Gerstenberger, B.S.; Ambler, C.; Arnold, E.P.; Banker, M.E.; Brown, M.F.; Clark, J.D.; Dermenci, A.; Dowty, M.E.; Fensome, A.; Fish, S.; Hayward, M.M.; Hegen, M.; Hollingshead, B.D.; Knafels, J.D.; Lin, D.W.; Lin, T.H.; Owen, D.R.; Saiah, E.; Sharma, R.; Vajdos, F.F.; Xing, L.; Yang, X.; Yang, X.; Wright, S.W. Discovery of tyrosine kinase 2 (TYK2) inhibitor (PF-06826647) for the treatment of autoimmune diseases. J. Med. Chem., 2020, 63(22), 13561-13577.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00948] [PMID: 32787094]
[98]
Krueger, J.G.; McInnes, I.B.; Blauvelt, A. Tyrosine kinase 2 and Janus kinase‒signal transducer and activator of transcription signaling and inhibition in plaque psoriasis. J. Am. Acad. Dermatol., 2022, 86(1), 148-157.
[http://dx.doi.org/10.1016/j.jaad.2021.06.869] [PMID: 34224773]
[99]
Tanaka, Y.; Okumura, H.; Kim, S.; Dorey, J.; Wojciechowski, P.; Chorąży, J.; Kato, D.; Schultz, N.M. Comparative efficacy and safety of peficitinib versus tofacitinib and baricitinib for treatment of rheumatoid arthritis: A systematic review and network meta-analysis. Rheumatol. Ther., 2021, 8(2), 729-750.
[http://dx.doi.org/10.1007/s40744-021-00284-1] [PMID: 33725321]
[100]
Kaneko, Y. Efficacy and safety of peficitinib in rheumatoid arthritis. Mod. Rheumatol., 2020, 30(5), 773-778.
[http://dx.doi.org/10.1080/14397595.2020.1794103] [PMID: 32643492]
[101]
Hamaguchi, H.; Amano, Y.; Moritomo, A.; Shirakami, S.; Nakajima, Y.; Nakai, K.; Nomura, N.; Ito, M.; Higashi, Y.; Inoue, T. Discovery and structural characterization of peficitinib (ASP015K) as a novel and potent JAK inhibitor. Bioorg. Med. Chem., 2018, 26(18), 4971-4983.
[http://dx.doi.org/10.1016/j.bmc.2018.08.005] [PMID: 30145050]
[102]
Akahane, K.; Li, Z.; Etchin, J.; Berezovskaya, A.; Gjini, E.; Masse, C.E.; Miao, W.; Rocnik, J.; Kapeller, R.; Greenwood, J.R.; Tiv, H.; Sanda, T.; Weinstock, D.M.; Look, A.T. Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia. Br. J. Haematol., 2017, 177(2), 271-282.
[http://dx.doi.org/10.1111/bjh.14563] [PMID: 28295194]
[103]
Norman, P. Selective JAK1 inhibitor and selective Tyk2 inhibitor patents. Expert Opin. Ther. Pat., 2012, 22(10), 1233-1249.
[http://dx.doi.org/10.1517/13543776.2012.723693] [PMID: 22971156]
[104]
Yogo, T.; Nagamiya, H.; Seto, M.; Sasaki, S.; Shih-Chung, H.; Ohba, Y.; Tokunaga, N.; Lee, G.N.; Rhim, C.Y.; Yoon, C.H.; Cho, S.Y.; Skene, R.; Yamamoto, S.; Satou, Y.; Kuno, M.; Miyazaki, T.; Nakagawa, H.; Okabe, A.; Marui, S.; Aso, K.; Yoshida, M. Structure-based design and synthesis of 3-amino-1,5-dihydro-4 H -pyrazolopyridin-4-one derivatives as tyrosine kinase 2 inhibitors. J. Med. Chem., 2016, 59(2), 733-749.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01857] [PMID: 26701356]
[105]
He, X.; Chen, X.; Zhang, H.; Xie, T.; Ye, X.Y. Selective Tyk2 inhibitors as potential therapeutic agents: a patent review (2015–2018). Expert Opin. Ther. Pat., 2019, 29(2), 137-149.
[http://dx.doi.org/10.1080/13543776.2019.1567713] [PMID: 30621465]
[106]
Gonzalez Lopez de Turiso, F.; Guckian, K. Selective TYK2 inhibitors as potential therapeutic agents: A patent review (2019–2021). Expert Opin. Ther. Pat., 2022, 32(4), 365-379.
[http://dx.doi.org/10.1080/13543776.2022.2026927] [PMID: 35001782]
[107]
Dymock, B.W.; See, C.S. Inhibitors of JAK2 and JAK3: an update on the patent literature 2010 – 2012. Expert Opin. Ther. Pat., 2013, 23(4), 449-501.
[http://dx.doi.org/10.1517/13543776.2013.765862] [PMID: 23367873]
[108]
Kettle, J.G.; Åstrand, A.; Catley, M.; Grimster, N.P.; Nilsson, M.; Su, Q.; Woessner, R. Inhibitors of JAK-family kinases: An update on the patent literature 2013-2015, part 1. Expert Opin. Ther. Pat., 2017, 27(2), 127-143.
[http://dx.doi.org/10.1080/13543776.2017.1252753] [PMID: 27774824]

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