application in cancer therapy and beyond. Therefore, we can expect many more
success stories from this field lying ahead of us.
Acknowledgments The author thanks Kristine Schmidt for language proofreading and editing.
Dr. Michael Forster, Dr. Marcel Günther, and Dr. Apirat Chaikuad are gratefully acknowledged for
fruitful discussion and suggestions. Dr. Apirat Chaikuad and Prof. Dr. Stefan Knapp are further
acknowledged for providing the data of their analysis of the protein kinases’ cysteinome. The author
appreciates financial support by the Postdoctoral Fellowship Program of the Baden-Württemberg
Stiftung, the Institutional Strategy of the University of Tübingen (ZUK 63, German Research
Foundation), the RiSC Program of the State Ministry of Baden-Württemberg for Sciences, Research
and Arts, and the Max Buchner Research Foundation.
Compliance and Ethical Standards
Conflict of Interest The author declares that he has no conflict of interest.
Funding While preparing the manuscript, the author received funding from the Postdoctoral
Fellowship Program of the Baden-Württemberg Stiftung, the Institutional Strategy of the University
of Tübingen (ZUK 63, German Research Foundation), the RiSC Program of the State Ministry of
Baden-Württemberg for Sciences, Research and Arts, and the Max Buchner Research Foundation.
Ethical Approval This article does not contain any studies with human participants or animals
performed by the author.
References
1. Singh J, Petter RC, Baillie TA, Whitty A (2011) The resurgence of covalent drugs. Nat Rev
Drug Discov 10:307–317. https://doi.org/10.1038/nrd3410
2. Bauer RA (2015) Covalent inhibitors in drug discovery: from accidental discoveries to
avoided liabilities and designed therapies. Drug Discov Today 20:1061–1073. https://doi.
org/10.1016/j.drudis.2015.05.005
3. Baillie TA (2016) Targeted covalent inhibitors for drug design. Angew Chem Int Ed
55:13408–13421. https://doi.org/10.1002/anie.201601091
4. Singh J, Petter RC, Kluge AF (2010) Targeted covalent drugs of the kinase family. Curr Opin
Chem Biol 14:475–480. https://doi.org/10.1016/j.cbpa.2010.06.168
5. Barf T, Kaptein A (2012) Irreversible protein kinase inhibitors: balancing the benefits and
risks. J Med Chem 55:6243–6262. https://doi.org/10.1021/jm3003203
6. Liu Q, Sabnis Y, Zhao Z, Zhang T, Buhrlage SJ, Jones LH, Gray NS (2013) Developing
irreversible inhibitors of the protein kinase Cysteinome. Chem Biol 20:146–159. https://doi.
org/10.1016/j.chembiol.2012.12.006
7. Chaikuad A, Koch P, Laufer SA, Knapp S (2018) The Cysteinome of protein kinases as a
target in drug development. Angew Chem Int Ed 57:4372–4385. https://doi.org/10.1002/anie.
201707875
8. de Cesco S, Kurian J, Dufresne C, Mittermaier AK, Moitessier N (2017) Covalent inhibitors
design and discovery. Eur J Med Chem 138:96–114. https://doi.org/10.1016/j.ejmech.2017.
06.019
9. Gehringer M, Laufer SA (2019) Emerging and re-emerging warheads for targeted covalent
inhibitors: applications in medicinal chemistry and chemical biology. J Med Chem
62:5673–5724. https://doi.org/10.1021/acs.jmedchem.8b01153
84
M. Gehringer
success stories from this field lying ahead of us.
Acknowledgments The author thanks Kristine Schmidt for language proofreading and editing.
Dr. Michael Forster, Dr. Marcel Günther, and Dr. Apirat Chaikuad are gratefully acknowledged for
fruitful discussion and suggestions. Dr. Apirat Chaikuad and Prof. Dr. Stefan Knapp are further
acknowledged for providing the data of their analysis of the protein kinases’ cysteinome. The author
appreciates financial support by the Postdoctoral Fellowship Program of the Baden-Württemberg
Stiftung, the Institutional Strategy of the University of Tübingen (ZUK 63, German Research
Foundation), the RiSC Program of the State Ministry of Baden-Württemberg for Sciences, Research
and Arts, and the Max Buchner Research Foundation.
Compliance and Ethical Standards
Conflict of Interest The author declares that he has no conflict of interest.
Funding While preparing the manuscript, the author received funding from the Postdoctoral
Fellowship Program of the Baden-Württemberg Stiftung, the Institutional Strategy of the University
of Tübingen (ZUK 63, German Research Foundation), the RiSC Program of the State Ministry of
Baden-Württemberg for Sciences, Research and Arts, and the Max Buchner Research Foundation.
Ethical Approval This article does not contain any studies with human participants or animals
performed by the author.
References
1. Singh J, Petter RC, Baillie TA, Whitty A (2011) The resurgence of covalent drugs. Nat Rev
Drug Discov 10:307–317. https://doi.org/10.1038/nrd3410
2. Bauer RA (2015) Covalent inhibitors in drug discovery: from accidental discoveries to
avoided liabilities and designed therapies. Drug Discov Today 20:1061–1073. https://doi.
org/10.1016/j.drudis.2015.05.005
3. Baillie TA (2016) Targeted covalent inhibitors for drug design. Angew Chem Int Ed
55:13408–13421. https://doi.org/10.1002/anie.201601091
4. Singh J, Petter RC, Kluge AF (2010) Targeted covalent drugs of the kinase family. Curr Opin
Chem Biol 14:475–480. https://doi.org/10.1016/j.cbpa.2010.06.168
5. Barf T, Kaptein A (2012) Irreversible protein kinase inhibitors: balancing the benefits and
risks. J Med Chem 55:6243–6262. https://doi.org/10.1021/jm3003203
6. Liu Q, Sabnis Y, Zhao Z, Zhang T, Buhrlage SJ, Jones LH, Gray NS (2013) Developing
irreversible inhibitors of the protein kinase Cysteinome. Chem Biol 20:146–159. https://doi.
org/10.1016/j.chembiol.2012.12.006
7. Chaikuad A, Koch P, Laufer SA, Knapp S (2018) The Cysteinome of protein kinases as a
target in drug development. Angew Chem Int Ed 57:4372–4385. https://doi.org/10.1002/anie.
201707875
8. de Cesco S, Kurian J, Dufresne C, Mittermaier AK, Moitessier N (2017) Covalent inhibitors
design and discovery. Eur J Med Chem 138:96–114. https://doi.org/10.1016/j.ejmech.2017.
06.019
9. Gehringer M, Laufer SA (2019) Emerging and re-emerging warheads for targeted covalent
inhibitors: applications in medicinal chemistry and chemical biology. J Med Chem
62:5673–5724. https://doi.org/10.1021/acs.jmedchem.8b01153
84
M. Gehringer