11. Sohn SJ, Forbush KA, Nguyen N, Witthuhn B, Nosaka T, Ihle JN, Perlmutter RM (1998)
Requirement for Jak3 in mature T cells: its role in regulation of T cell homeostasis. J Immunol
160:2130–2138
12. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW,
Leonard WJ (1993) Interleukin-2 receptor γ chain mutation results in X-linked severe
combined immunodeficiency in humans. Cell 73:147–157. https://doi.org/10.1016/0092-8674
(93)90167-O
13. Pesu M, Laurence A, Kishore N, Zwillich SH, Chan G, O’Shea JJ (2008) Therapeutic targeting
of Janus kinases. Immunol Rev 223:132–142. https://doi.org/10.1111/j.1600-065X.2008.
00644.x
14. Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ,
Sawyer PS, Perry BD, Brissette WH, McCurdy SP, Kudlacz EM, Conklyn MJ, Elliott EA,
Koslov ER, Fisher MB, Strelevitz TJ, Yoon K, Whipple DA, Sun J, Munchhof MJ, Doty JL,
Casavant JM, Blumenkopf TA, Hines M, Brown MF, Lillie BM, Subramanyam C,
Shang-Poa C, Milici AJ, Beckius GE, Moyer JD, Su C, Woodworth TG, Gaweco AS,
Beals CR, Littman BH, Fisher DA, Smith JF, Zagouras P, Magna HA, Saltarelli MJ,
Johnson KS, Nelms LF, Etages SGD, Hayes LS, Kawabata TT, Finco-Kent D, Baker DL,
Larson M, Si M-S, Paniagua R, Higgins J, Holm B, Reitz B, Zhou Y-J, Morris RE, O’Shea JJ,
Borie DC (2003) Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor.
Science 302:875–878. https://doi.org/10.1126/science.1087061
15. Garber K (2013) Pfizer’s first-in-class JAK inhibitor pricey for rheumatoid arthritis market.
Nat Biotech 31:3–4. https://doi.org/10.1038/nbt0113-3
16. Thoma G, Drückes P, Zerwes H-G (2014) Selective inhibitors of the Janus kinase Jak3 – are they
effective? Bioorg Med Chem Lett 24:4617–4621. https://doi.org/10.1016/j.bmcl.2014.08.046
17. Press Announcements - FDA approves new treatment for moderately to severely
active ulcerative colitis. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm609225.htm. Accessed 18 Oct 2018
18. Xeljanz. European Medicines Agency. https://www.ema.europa.eu/medicines/human/EPAR/
xeljanz. Accessed 18 Oct 2018
19. Markham A (2017) Baricitinib: first global approval. Drugs 77:697–704. https://doi.org/10.
1007/s40265-017-0723-3
20. Mullard A (2018) FDA approves Eli Lilly’s baricitinib. Nat Rev Drug Discov 17:460
21. Mesa RA, Yasothan U, Kirkpatrick P (2012) Ruxolitinib. Nat Rev Drug Discov 11:103–104.
https://doi.org/10.1038/nrd3652
22. Gonzales AJ, Bowman JW, Fici GJ, Zhang M, Mann DW, Mitton-Fry M (2014)
Oclacitinib (APOQUEL
®
) is a novel Janus kinase inhibitor with activity against cytokines
involved in allergy. J Vet Pharmacol Ther 37:317–324. https://doi.org/10.1111/jvp.12101
23. Thoma G, Nuninger F, Falchetto R, Hermes E, Tavares GA, Vangrevelinghe E, Zerwes H-G
(2010) Identification of a potent Janus kinase 3 inhibitor with high selectivity within the
Janus kinase family. J Med Chem 54:284–288. https://doi.org/10.1021/jm101157q
24. Lin TH, Hegen M, Quadros E, Nickerson-Nutter CL, Appell KC, Cole AG, Shao Y, Tam S,
Ohlmeyer M, Wang B, Goodwin DG, Kimble EF, Quintero J, Gao M, Symanowicz P,
Wrocklage C, Lussier J, Schelling SH, Hewet AG, Xuan D, Krykbaev R, Togias J, Xu X,
Harrison R, Mansour T, Collins M, Clark JD, Webb ML, Seidl KJ (2010) Selective functional
inhibition of JAK-3 is sufficient for efficacy in collagen-induced arthritis in mice. Arthritis
Rheum 62:2283–2293. https://doi.org/10.1002/art.27536
25. Farmer LJ, Ledeboer MW, Hoock T, Arnost MJ, Bethiel RS, Bennani YL, Black JJ, Brummel CL,
Chakilam A, Dorsch WA, Fan B, Cochran JE, Halas S, Harrington EM, Hogan JK, Howe D,
Huang H, Jacobs DH, Laitinen LM, Liao S, Mahajan S, Marone V, Martinez-Botella G,
McCarthy P, Messersmith D, Namchuk M, Oh L, Penney MS, Pierce AC, Raybuck SA,
Rugg A, Salituro FG, Saxena K, Shannon D, Shlyakter D, Swenson L, Tian S-K, Town C,
Wang J, Wang T, Wannamaker MW, Winquist RJ, Zuccola HJ (2015) Discovery of VX-509
Covalent Janus Kinase 3 Inhibitors
253
Requirement for Jak3 in mature T cells: its role in regulation of T cell homeostasis. J Immunol
160:2130–2138
12. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW,
Leonard WJ (1993) Interleukin-2 receptor γ chain mutation results in X-linked severe
combined immunodeficiency in humans. Cell 73:147–157. https://doi.org/10.1016/0092-8674
(93)90167-O
13. Pesu M, Laurence A, Kishore N, Zwillich SH, Chan G, O’Shea JJ (2008) Therapeutic targeting
of Janus kinases. Immunol Rev 223:132–142. https://doi.org/10.1111/j.1600-065X.2008.
00644.x
14. Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ,
Sawyer PS, Perry BD, Brissette WH, McCurdy SP, Kudlacz EM, Conklyn MJ, Elliott EA,
Koslov ER, Fisher MB, Strelevitz TJ, Yoon K, Whipple DA, Sun J, Munchhof MJ, Doty JL,
Casavant JM, Blumenkopf TA, Hines M, Brown MF, Lillie BM, Subramanyam C,
Shang-Poa C, Milici AJ, Beckius GE, Moyer JD, Su C, Woodworth TG, Gaweco AS,
Beals CR, Littman BH, Fisher DA, Smith JF, Zagouras P, Magna HA, Saltarelli MJ,
Johnson KS, Nelms LF, Etages SGD, Hayes LS, Kawabata TT, Finco-Kent D, Baker DL,
Larson M, Si M-S, Paniagua R, Higgins J, Holm B, Reitz B, Zhou Y-J, Morris RE, O’Shea JJ,
Borie DC (2003) Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor.
Science 302:875–878. https://doi.org/10.1126/science.1087061
15. Garber K (2013) Pfizer’s first-in-class JAK inhibitor pricey for rheumatoid arthritis market.
Nat Biotech 31:3–4. https://doi.org/10.1038/nbt0113-3
16. Thoma G, Drückes P, Zerwes H-G (2014) Selective inhibitors of the Janus kinase Jak3 – are they
effective? Bioorg Med Chem Lett 24:4617–4621. https://doi.org/10.1016/j.bmcl.2014.08.046
17. Press Announcements - FDA approves new treatment for moderately to severely
active ulcerative colitis. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm609225.htm. Accessed 18 Oct 2018
18. Xeljanz. European Medicines Agency. https://www.ema.europa.eu/medicines/human/EPAR/
xeljanz. Accessed 18 Oct 2018
19. Markham A (2017) Baricitinib: first global approval. Drugs 77:697–704. https://doi.org/10.
1007/s40265-017-0723-3
20. Mullard A (2018) FDA approves Eli Lilly’s baricitinib. Nat Rev Drug Discov 17:460
21. Mesa RA, Yasothan U, Kirkpatrick P (2012) Ruxolitinib. Nat Rev Drug Discov 11:103–104.
https://doi.org/10.1038/nrd3652
22. Gonzales AJ, Bowman JW, Fici GJ, Zhang M, Mann DW, Mitton-Fry M (2014)
Oclacitinib (APOQUEL
®
) is a novel Janus kinase inhibitor with activity against cytokines
involved in allergy. J Vet Pharmacol Ther 37:317–324. https://doi.org/10.1111/jvp.12101
23. Thoma G, Nuninger F, Falchetto R, Hermes E, Tavares GA, Vangrevelinghe E, Zerwes H-G
(2010) Identification of a potent Janus kinase 3 inhibitor with high selectivity within the
Janus kinase family. J Med Chem 54:284–288. https://doi.org/10.1021/jm101157q
24. Lin TH, Hegen M, Quadros E, Nickerson-Nutter CL, Appell KC, Cole AG, Shao Y, Tam S,
Ohlmeyer M, Wang B, Goodwin DG, Kimble EF, Quintero J, Gao M, Symanowicz P,
Wrocklage C, Lussier J, Schelling SH, Hewet AG, Xuan D, Krykbaev R, Togias J, Xu X,
Harrison R, Mansour T, Collins M, Clark JD, Webb ML, Seidl KJ (2010) Selective functional
inhibition of JAK-3 is sufficient for efficacy in collagen-induced arthritis in mice. Arthritis
Rheum 62:2283–2293. https://doi.org/10.1002/art.27536
25. Farmer LJ, Ledeboer MW, Hoock T, Arnost MJ, Bethiel RS, Bennani YL, Black JJ, Brummel CL,
Chakilam A, Dorsch WA, Fan B, Cochran JE, Halas S, Harrington EM, Hogan JK, Howe D,
Huang H, Jacobs DH, Laitinen LM, Liao S, Mahajan S, Marone V, Martinez-Botella G,
McCarthy P, Messersmith D, Namchuk M, Oh L, Penney MS, Pierce AC, Raybuck SA,
Rugg A, Salituro FG, Saxena K, Shannon D, Shlyakter D, Swenson L, Tian S-K, Town C,
Wang J, Wang T, Wannamaker MW, Winquist RJ, Zuccola HJ (2015) Discovery of VX-509
Covalent Janus Kinase 3 Inhibitors
253