95. Koch A, Rode HB, Richters A, Rauh D, Hauf S (2012) A chemical genetic approach for
covalent inhibition of analogue-sensitive Aurora kinase. ACS Chem Biol 7:723–731. https://
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96. Blair JA, Rauh D, Kung C, Yun C-H, Fan Q-W, Rode H, Zhang C, Eck MJ, Weiss WA,
Shokat KM (2007) Structure-guided development of affinity probes for tyrosine kinases using
chemical genetics. Nat Chem Biol 3:229–238. https://doi.org/10.1038/nchembio866
97. Zhang T, Inesta-Vaquera F, Niepel M, Zhang J, Ficarro SB, Machleidt T, Xie T, Marto JA,
Kim N, Sim T, Laughlin JD, Park H, LoGrasso PV, Patricelli M, Nomanbhoy TK, Sorger PK,
Alessi DR, Gray NS (2012) Discovery of potent and selective covalent inhibitors of JNK.
Chem Biol 19:140–154. https://doi.org/10.1016/j.chembiol.2011.11.010
98. Muth F, El-Gokha A, Ansideri F, Eitel M, Döring E, Sievers-Engler A, Lange A, Boeckler
FM, Lämmerhofer M, Koch P, Laufer SA (2017) Tri- and tetrasubstituted pyridinylimidazoles
as covalent inhibitors of c-Jun N-terminal kinase 3. J Med Chem 60:594–607. https://doi.org/
10.1021/acs.jmedchem.6b01180
99. Koch P, Gehringer M, Laufer SA (2015) Inhibitors of c-Jun N-terminal kinases: an update. J
Med Chem 58:72–95. https://doi.org/10.1021/jm501212r
100. Gehringer M, Muth F, Koch P, Laufer SA (2015) c-Jun N-terminal kinase inhibitors: a patent
review (2010–2014). Expert Opin Ther Patents 25:849–872. https://doi.org/10.1517/
13543776.2015.1039984
101. Kung A, Chen Y-C, Schimpl M, Ni F, Zhu J, Turner M, Molina H, Overman R, Zhang C
(2016) Development of specific, irreversible inhibitors for a receptor tyrosine kinase EphB3. J
Am Chem Soc 138:10554–10560. https://doi.org/10.1021/jacs.6b05483
102. Kung A, Schimpl M, Ekanayake A, Chen Y-C, Overman R, Zhang C (2017) A chemicalgenetic approach to generate selective covalent inhibitors of protein kinases. ACS Chem Biol
12:1499–1503. https://doi.org/10.1021/acschembio.6b01083
103. Nacht M, Qiao L, Sheets MP, St. Martin T, Labenski M, Mazdiyasni H, Karp R, Zhu Z,
Chaturvedi P, Bhavsar D, Niu D, Westlin W, Petter RC, Medikonda AP, Singh J (2013)
Discovery of a potent and isoform-selective targeted covalent inhibitor of the lipid kinase
PI3Kα. J Med Chem 56:712–721. https://doi.org/10.1021/jm3008745
104. Xie T, Lim SM, Westover KD, Dodge ME, Ercan D, Ficarro SB, Udayakumar D, Gurbani D,
Tae HS, Riddle SM, Sim T, Marto JA, Jänne PA, Crews CM, Gray NS (2014) Pharmacological targeting of the pseudokinase Her3. Nat Chem Biol 10:1006–1012. https://doi.org/10.
1038/nchembio.1658
105. Tinworth CP, Lithgow H, Dittus L, Bassi ZI, Hughes SE, Muelbaier M, Dai H, Smith IED,
Kerr WJ, Burley GA, Bantscheff M, Harling JD (2019) PROTAC-mediated degradation of
Bruton’s tyrosine kinase is inhibited by covalent binding. ACS Chem Biol 14:342–347.
https://doi.org/10.1021/acschembio.8b01094
106. Cohen MS, Zhang C, Shokat KM, Taunton J (2005) Structural bioinformatics-based design of
selective, irreversible kinase inhibitors. Science 308:1318–1321. https://doi.org/10.1126/
science1108367
107. Cohen MS, Hadjivassiliou H, Taunton J (2007) A clickable inhibitor reveals contextdependent autoactivation of p90 RSK. Nat Chem Biol 3:156–160. https://doi.org/10.1038/
nchembio859
108. Miller RM, Paavilainen VO, Krishnan S, Serafimova IM, Taunton J (2013) Electrophilic
fragment-based design of reversible covalent kinase inhibitors. J Am Chem Soc
135:5298–5301. https://doi.org/10.1021/ja401221b
109. Lebraud H, Coxon CR, Archard SV, Bawn MC, Carbain B, Matheson JC, Turner MD,
Cano C, Griffin JR, Hardcastle RI, Baisch U, Harrington WR, Golding TB (2014) Model
system for irreversible inhibition of Nek2: thiol addition to ethynylpurines and related
substituted heterocycles. Org Biomol Chem 12:141–148. https://doi.org/10.1039/
C3OB41806E
110. Mitcheson DF, Bottrill AR, Carr K, Coxon CR, Cano C, Golding BT, Griffin RJ, Fry AM,
Doerig C, Bayliss R, Tobin AB (2016) A new tool for the chemical genetic investigation of the
Covalent Kinase Inhibitors: An Overview
91
covalent inhibition of analogue-sensitive Aurora kinase. ACS Chem Biol 7:723–731. https://
doi.org/10.1021/cb200465c
96. Blair JA, Rauh D, Kung C, Yun C-H, Fan Q-W, Rode H, Zhang C, Eck MJ, Weiss WA,
Shokat KM (2007) Structure-guided development of affinity probes for tyrosine kinases using
chemical genetics. Nat Chem Biol 3:229–238. https://doi.org/10.1038/nchembio866
97. Zhang T, Inesta-Vaquera F, Niepel M, Zhang J, Ficarro SB, Machleidt T, Xie T, Marto JA,
Kim N, Sim T, Laughlin JD, Park H, LoGrasso PV, Patricelli M, Nomanbhoy TK, Sorger PK,
Alessi DR, Gray NS (2012) Discovery of potent and selective covalent inhibitors of JNK.
Chem Biol 19:140–154. https://doi.org/10.1016/j.chembiol.2011.11.010
98. Muth F, El-Gokha A, Ansideri F, Eitel M, Döring E, Sievers-Engler A, Lange A, Boeckler
FM, Lämmerhofer M, Koch P, Laufer SA (2017) Tri- and tetrasubstituted pyridinylimidazoles
as covalent inhibitors of c-Jun N-terminal kinase 3. J Med Chem 60:594–607. https://doi.org/
10.1021/acs.jmedchem.6b01180
99. Koch P, Gehringer M, Laufer SA (2015) Inhibitors of c-Jun N-terminal kinases: an update. J
Med Chem 58:72–95. https://doi.org/10.1021/jm501212r
100. Gehringer M, Muth F, Koch P, Laufer SA (2015) c-Jun N-terminal kinase inhibitors: a patent
review (2010–2014). Expert Opin Ther Patents 25:849–872. https://doi.org/10.1517/
13543776.2015.1039984
101. Kung A, Chen Y-C, Schimpl M, Ni F, Zhu J, Turner M, Molina H, Overman R, Zhang C
(2016) Development of specific, irreversible inhibitors for a receptor tyrosine kinase EphB3. J
Am Chem Soc 138:10554–10560. https://doi.org/10.1021/jacs.6b05483
102. Kung A, Schimpl M, Ekanayake A, Chen Y-C, Overman R, Zhang C (2017) A chemicalgenetic approach to generate selective covalent inhibitors of protein kinases. ACS Chem Biol
12:1499–1503. https://doi.org/10.1021/acschembio.6b01083
103. Nacht M, Qiao L, Sheets MP, St. Martin T, Labenski M, Mazdiyasni H, Karp R, Zhu Z,
Chaturvedi P, Bhavsar D, Niu D, Westlin W, Petter RC, Medikonda AP, Singh J (2013)
Discovery of a potent and isoform-selective targeted covalent inhibitor of the lipid kinase
PI3Kα. J Med Chem 56:712–721. https://doi.org/10.1021/jm3008745
104. Xie T, Lim SM, Westover KD, Dodge ME, Ercan D, Ficarro SB, Udayakumar D, Gurbani D,
Tae HS, Riddle SM, Sim T, Marto JA, Jänne PA, Crews CM, Gray NS (2014) Pharmacological targeting of the pseudokinase Her3. Nat Chem Biol 10:1006–1012. https://doi.org/10.
1038/nchembio.1658
105. Tinworth CP, Lithgow H, Dittus L, Bassi ZI, Hughes SE, Muelbaier M, Dai H, Smith IED,
Kerr WJ, Burley GA, Bantscheff M, Harling JD (2019) PROTAC-mediated degradation of
Bruton’s tyrosine kinase is inhibited by covalent binding. ACS Chem Biol 14:342–347.
https://doi.org/10.1021/acschembio.8b01094
106. Cohen MS, Zhang C, Shokat KM, Taunton J (2005) Structural bioinformatics-based design of
selective, irreversible kinase inhibitors. Science 308:1318–1321. https://doi.org/10.1126/
science1108367
107. Cohen MS, Hadjivassiliou H, Taunton J (2007) A clickable inhibitor reveals contextdependent autoactivation of p90 RSK. Nat Chem Biol 3:156–160. https://doi.org/10.1038/
nchembio859
108. Miller RM, Paavilainen VO, Krishnan S, Serafimova IM, Taunton J (2013) Electrophilic
fragment-based design of reversible covalent kinase inhibitors. J Am Chem Soc
135:5298–5301. https://doi.org/10.1021/ja401221b
109. Lebraud H, Coxon CR, Archard SV, Bawn MC, Carbain B, Matheson JC, Turner MD,
Cano C, Griffin JR, Hardcastle RI, Baisch U, Harrington WR, Golding TB (2014) Model
system for irreversible inhibition of Nek2: thiol addition to ethynylpurines and related
substituted heterocycles. Org Biomol Chem 12:141–148. https://doi.org/10.1039/
C3OB41806E
110. Mitcheson DF, Bottrill AR, Carr K, Coxon CR, Cano C, Golding BT, Griffin RJ, Fry AM,
Doerig C, Bayliss R, Tobin AB (2016) A new tool for the chemical genetic investigation of the
Covalent Kinase Inhibitors: An Overview
91