39. Ross JA, Spadaro M, Rosado DC, Cavallo F, Kirken RA, Pericle F (2014) Inhibition of JAK3
with a novel, selective and orally active small molecule induces therapeutic response in T-cell
malignancies. Leukemia 28:941–944. https://doi.org/10.1038/leu.2013.309
40. Styles M, Zeng J, Treutlein H, Wilks A, Kling M, Bu X, Burns C (2005) Selective kinase
inhibitors
41. Goedken ER, Argiriadi MA, Banach DL, Fiamengo BA, Foley SE, Frank KE, George JS,
Harris CM, Hobson AD, Ihle DC, Marcotte D, Merta PJ, Michalak ME, Murdock SE,
Tomlinson MJ, Voss JW (2015) Tricyclic covalent inhibitors selectively target Jak3 through
an active site thiol. J Biol Chem 290:4573–4589. https://doi.org/10.1074/jbc.M114.595181
42. Goldstein DM, Brameld KA, Verner E (2012) Azaindole derivatives as tyrosine kinase
inhibitors
43. Goldstein D, Brameld K, Owens T (2014) Azaindole derivatives as JAK3 inhibitors
44. Ahearn S, Christopher M, Jung J, Pu Q, Rivkin A, Scott M, Witter D, Woo HC, Cash B,
Dinsmore C, Guerin D (2013) Pyrrolopyrimidines as Janus kinase inhibitors
45. Smith GA, Uchida K, Weiss A, Taunton J (2016) Essential biphasic role for JAK3 catalytic
activity in IL-2 receptor signaling. Nat Chem Biol 12:373–379. https://doi.org/10.1038/
nchembio.2056
46. London N, Miller RM, Krishnan S, Uchida K, Irwin JJ, Eidam O, Gibold L, Cimermančič P,
Bonnet R, Shoichet BK, Taunton J (2014) Covalent docking of large libraries for the discovery
of chemical probes. Nat Chem Biol 10:1066–1072. https://doi.org/10.1038/nchembio.1666
47. Gehringer M, Forster M, Laufer SA (2015) Solution-phase parallel synthesis of Ruxolitinibderived Janus kinase inhibitors via copper-catalyzed Azide–Alkyne cycloaddition. ACS Comb
Sci 17:5–10. https://doi.org/10.1021/co500122h
48. Forster M, Chaikuad A, Bauer SM, Holstein J, Robers MB, Corona CR, Gehringer M,
Pfaffenrot E, Ghoreschi K, Knapp S, Laufer SA (2016) Selective JAK3 inhibitors with a
covalent reversible binding mode targeting a new induced fit binding pocket. Cell Chem
Biol 23:1335–1340. https://doi.org/10.1016/j.chembiol.2016.10.008
49. Tan L, Akahane K, McNally R, Reyskens KMSE, Ficarro SB, Liu S, Herter-Sprie GS,
Koyama S, Pattison MJ, Labella K, Johannessen L, Akbay EA, Wong K-K, Frank DA,
Marto JA, Look TA, Arthur JSC, Eck MJ, Gray NS (2015) Development of selective covalent
Janus kinase 3 inhibitors. J Med Chem 58:6589–6606. https://doi.org/10.1021/acs.jmedchem.
5b00710
50. Zhou W, Ercan D, Chen L, Yun C-H, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE,
Padera R, Engen JR, Wong K-K, Eck MJ, Gray NS, Jänne PA (2009) Novel mutant-selective
EGFR kinase inhibitors against EGFR T790M. Nature 462:1070–1074. https://doi.org/10.
1038/nature08622
51. Ge Y, Wang C, Song S, Huang J, Liu Z, Li Y, Meng Q, Zhang J, Yao J, Liu K, Ma X, Sun X
(2018) Identification of highly potent BTK and JAK3 dual inhibitors with improved activity for
the treatment of B-cell lymphoma. Eur J Med Chem 143:1847–1857. https://doi.org/10.1016/j.
ejmech.2017.10.080
52. Elwood F, Witter DJ, Piesvaux J, Kraybill B, Bays N, Alpert C, Goldenblatt P, Qu Y,
Ivanovska I, Lee H-H, Chiu C-S, Tang H, Scott ME, Deshmukh SV, Zielstorff M, Byford A,
Chakravarthy K, Dorosh L, Rivkin A, Klappenbach J, Pan B-S, Kariv I, Dinsmore C, Slipetz D,
Dandliker PJ (2017) Evaluation of JAK3 biology in autoimmune disease using a highly
selective, irreversible JAK3 inhibitor. J Pharmacol Exp Ther 361:229–244. https://doi.org/10.
1124/jpet.116.239723
53. Forster M, Chaikuad A, Dimitrov T, Döring E, Holstein J, Berger B-T, Gehringer M,
Ghoreschi K, Müller S, Knapp S, Laufer SA (2018) Development, optimization, and structure–
activity relationships of covalent-reversible JAK3 inhibitors based on a tricyclic Imidazo[5,4-d]
pyrrolo[2,3-b]pyridine scaffold. J Med Chem 61:5350–5366. https://doi.org/10.1021/acs.
jmedchem.8b00571
54. Kulagowski JJ, Blair W, Bull RJ, Chang C, Deshmukh G, Dyke HJ, Eigenbrot C, Ghilardi N,
Gibbons P, Harrison TK, Hewitt PR, Liimatta M, Hurley CA, Johnson A, Johnson T, Kenny JR,
Covalent Janus Kinase 3 Inhibitors
255
with a novel, selective and orally active small molecule induces therapeutic response in T-cell
malignancies. Leukemia 28:941–944. https://doi.org/10.1038/leu.2013.309
40. Styles M, Zeng J, Treutlein H, Wilks A, Kling M, Bu X, Burns C (2005) Selective kinase
inhibitors
41. Goedken ER, Argiriadi MA, Banach DL, Fiamengo BA, Foley SE, Frank KE, George JS,
Harris CM, Hobson AD, Ihle DC, Marcotte D, Merta PJ, Michalak ME, Murdock SE,
Tomlinson MJ, Voss JW (2015) Tricyclic covalent inhibitors selectively target Jak3 through
an active site thiol. J Biol Chem 290:4573–4589. https://doi.org/10.1074/jbc.M114.595181
42. Goldstein DM, Brameld KA, Verner E (2012) Azaindole derivatives as tyrosine kinase
inhibitors
43. Goldstein D, Brameld K, Owens T (2014) Azaindole derivatives as JAK3 inhibitors
44. Ahearn S, Christopher M, Jung J, Pu Q, Rivkin A, Scott M, Witter D, Woo HC, Cash B,
Dinsmore C, Guerin D (2013) Pyrrolopyrimidines as Janus kinase inhibitors
45. Smith GA, Uchida K, Weiss A, Taunton J (2016) Essential biphasic role for JAK3 catalytic
activity in IL-2 receptor signaling. Nat Chem Biol 12:373–379. https://doi.org/10.1038/
nchembio.2056
46. London N, Miller RM, Krishnan S, Uchida K, Irwin JJ, Eidam O, Gibold L, Cimermančič P,
Bonnet R, Shoichet BK, Taunton J (2014) Covalent docking of large libraries for the discovery
of chemical probes. Nat Chem Biol 10:1066–1072. https://doi.org/10.1038/nchembio.1666
47. Gehringer M, Forster M, Laufer SA (2015) Solution-phase parallel synthesis of Ruxolitinibderived Janus kinase inhibitors via copper-catalyzed Azide–Alkyne cycloaddition. ACS Comb
Sci 17:5–10. https://doi.org/10.1021/co500122h
48. Forster M, Chaikuad A, Bauer SM, Holstein J, Robers MB, Corona CR, Gehringer M,
Pfaffenrot E, Ghoreschi K, Knapp S, Laufer SA (2016) Selective JAK3 inhibitors with a
covalent reversible binding mode targeting a new induced fit binding pocket. Cell Chem
Biol 23:1335–1340. https://doi.org/10.1016/j.chembiol.2016.10.008
49. Tan L, Akahane K, McNally R, Reyskens KMSE, Ficarro SB, Liu S, Herter-Sprie GS,
Koyama S, Pattison MJ, Labella K, Johannessen L, Akbay EA, Wong K-K, Frank DA,
Marto JA, Look TA, Arthur JSC, Eck MJ, Gray NS (2015) Development of selective covalent
Janus kinase 3 inhibitors. J Med Chem 58:6589–6606. https://doi.org/10.1021/acs.jmedchem.
5b00710
50. Zhou W, Ercan D, Chen L, Yun C-H, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE,
Padera R, Engen JR, Wong K-K, Eck MJ, Gray NS, Jänne PA (2009) Novel mutant-selective
EGFR kinase inhibitors against EGFR T790M. Nature 462:1070–1074. https://doi.org/10.
1038/nature08622
51. Ge Y, Wang C, Song S, Huang J, Liu Z, Li Y, Meng Q, Zhang J, Yao J, Liu K, Ma X, Sun X
(2018) Identification of highly potent BTK and JAK3 dual inhibitors with improved activity for
the treatment of B-cell lymphoma. Eur J Med Chem 143:1847–1857. https://doi.org/10.1016/j.
ejmech.2017.10.080
52. Elwood F, Witter DJ, Piesvaux J, Kraybill B, Bays N, Alpert C, Goldenblatt P, Qu Y,
Ivanovska I, Lee H-H, Chiu C-S, Tang H, Scott ME, Deshmukh SV, Zielstorff M, Byford A,
Chakravarthy K, Dorosh L, Rivkin A, Klappenbach J, Pan B-S, Kariv I, Dinsmore C, Slipetz D,
Dandliker PJ (2017) Evaluation of JAK3 biology in autoimmune disease using a highly
selective, irreversible JAK3 inhibitor. J Pharmacol Exp Ther 361:229–244. https://doi.org/10.
1124/jpet.116.239723
53. Forster M, Chaikuad A, Dimitrov T, Döring E, Holstein J, Berger B-T, Gehringer M,
Ghoreschi K, Müller S, Knapp S, Laufer SA (2018) Development, optimization, and structure–
activity relationships of covalent-reversible JAK3 inhibitors based on a tricyclic Imidazo[5,4-d]
pyrrolo[2,3-b]pyridine scaffold. J Med Chem 61:5350–5366. https://doi.org/10.1021/acs.
jmedchem.8b00571
54. Kulagowski JJ, Blair W, Bull RJ, Chang C, Deshmukh G, Dyke HJ, Eigenbrot C, Ghilardi N,
Gibbons P, Harrison TK, Hewitt PR, Liimatta M, Hurley CA, Johnson A, Johnson T, Kenny JR,
Covalent Janus Kinase 3 Inhibitors
255