27. Serafimova IM, Pufall MA, Krishnan S, Duda K, Cohen MS, Maglathlin RL, McFarland JM,
Miller RM, Frödin M, Taunton J (2012) Reversible targeting of noncatalytic cysteines with
chemically tuned electrophiles. Nat Chem Biol 8:471–476. https://doi.org/10.1038/nchembio.
925
28. Krishnan S, Miller RM, Tian B, Mullins RD, Jacobson MP, Taunton J (2014) Design of
reversible, cysteine-targeted Michael acceptors guided by kinetic and computational analysis.
J Am Chem Soc 136:12624–12630. https://doi.org/10.1021/ja505194w
29. Knoepfel T, Furet P, Mah R, Buschmann N, Leblanc C, Ripoche S, Graus-Porta D,
Wartmann M, Galuba I, Fairhurst RA (2018) 2-formylpyridyl ureas as highly selective
reversible-covalent inhibitors of fibroblast growth factor receptor 4. ACS Med Chem Lett
9:215–220. https://doi.org/10.1021/acsmedchemlett.7b00485
30. Müller J, Kirschner RA, Geyer A, Klebe G (2019) Conceptional design of self-assembling
bisubstrate-like inhibitors of protein kinase A resulting in a Boronic acid glutamate linkage.
ACS Omega 4:775–784. https://doi.org/10.1021/acsomega.8b02364
31. Shindo N, Fuchida H, Sato M, Watari K, Shibata T, Kuwata K, Miura C, Okamoto K,
Hatsuyama Y, Tokunaga K, Sakamoto S, Morimoto S, Abe Y, Shiroishi M, Caaveiro JMM,
Ueda T, Tamura T, Matsunaga N, Nakao T, Koyanagi S, Ohdo S, Yamaguchi Y, Hamachi I,
Ono M, Ojida A (2019) Selective and reversible modification of kinase cysteines with
chlorofluoroacetamides. Nat Chem Biol 15:250. https://doi.org/10.1038/s41589-018-0204-3
32. Zhang J, Yang PL, Gray NS (2009) Targeting cancer with small molecule kinase inhibitors.
Nat Rev Cancer 9:28–39. https://doi.org/10.1038/nrc2559
33. Traxler P (1998) Tyrosine kinase inhibitors in cancer treatment (part II). Expert Opin Ther Pat
8:1599–1625. https://doi.org/10.1517/13543776.8.12.1599
34. Traxler P, Furet P (1999) Strategies toward the design of novel and selective protein tyrosine
kinase inhibitors. Pharmacol Ther 82:195–206. https://doi.org/10.1016/S0163-7258(98)
00044-8
35. Backes A, Zech B, Felber B, Klebl B, Müller G (2008) Small-molecule inhibitors binding to
protein kinase. Part II: the novel pharmacophore approach of type II and type III inhibition.
Exp Opin Drug Discovery 3:1427–1449. https://doi.org/10.1517/17460440802580106
36. Liao JJ-L (2007) Molecular recognition of protein kinase binding pockets for design of potent
and selective kinase inhibitors. J Med Chem 50:409–424. https://doi.org/10.1021/jm0608107
37. Yoshida T, Kakizuka A, Imamura H (2016) BTeam, a novel BRET-based biosensor for the
accurate quantification of ATP concentration within living cells. Sci Rep 6:39618. https://doi.
org/10.1038/srep39618
38. Yen-Pon E, Li B, Acebrón-Garcia-de-Eulate M, Tomkiewicz-Raulet C, Dawson J, Lietha D,
Frame MC, Coumoul X, Garbay C, Etheve-Quelquejeu M, Chen H (2018) Structure-based
design, synthesis, and characterization of the first irreversible inhibitor of focal adhesion
kinase. ACS Chem Biol 13:2067–2073. https://doi.org/10.1021/acschembio.8b00250
39. Ferguson FM, Gray NS (2018) Kinase inhibitors: the road ahead. Nat Rev Drug Discov
17:353–377. https://doi.org/10.1038/nrd.2018.21
40. Zhao Z, Bourne PE (2018) Progress with covalent small-molecule kinase inhibitors. Drug
Discov Today 23:727–735. https://doi.org/10.1016/j.drudis.2018.01.035
41. Gilbert AM (2014) Recent advances in irreversible kinase inhibitors. Pharm Patent Anal
3:375–386. https://doi.org/10.4155/ppa.14.24
42. Sanderson K (2013) Irreversible kinase inhibitors gain traction. Nat Rev Drug Discov
12:649–651. https://doi.org/10.1038/nrd4103
43. Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, Flowers ME, Logan AC,
Nakamura R, Blazar BR, Li Y, Chang S, Lal I, Dubovsky J, James DF, Styles L, Jaglowski S
(2017) Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood
130:2243–2250. https://doi.org/10.1182/blood-2017-07-793786
44. Soria J-C, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH,
Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC,
Cheng Y, Cho EK, Voon PJ, Planchard D, Su W-C, Gray JE, Lee S-M, Hodge R,
86
M. Gehringer
Miller RM, Frödin M, Taunton J (2012) Reversible targeting of noncatalytic cysteines with
chemically tuned electrophiles. Nat Chem Biol 8:471–476. https://doi.org/10.1038/nchembio.
925
28. Krishnan S, Miller RM, Tian B, Mullins RD, Jacobson MP, Taunton J (2014) Design of
reversible, cysteine-targeted Michael acceptors guided by kinetic and computational analysis.
J Am Chem Soc 136:12624–12630. https://doi.org/10.1021/ja505194w
29. Knoepfel T, Furet P, Mah R, Buschmann N, Leblanc C, Ripoche S, Graus-Porta D,
Wartmann M, Galuba I, Fairhurst RA (2018) 2-formylpyridyl ureas as highly selective
reversible-covalent inhibitors of fibroblast growth factor receptor 4. ACS Med Chem Lett
9:215–220. https://doi.org/10.1021/acsmedchemlett.7b00485
30. Müller J, Kirschner RA, Geyer A, Klebe G (2019) Conceptional design of self-assembling
bisubstrate-like inhibitors of protein kinase A resulting in a Boronic acid glutamate linkage.
ACS Omega 4:775–784. https://doi.org/10.1021/acsomega.8b02364
31. Shindo N, Fuchida H, Sato M, Watari K, Shibata T, Kuwata K, Miura C, Okamoto K,
Hatsuyama Y, Tokunaga K, Sakamoto S, Morimoto S, Abe Y, Shiroishi M, Caaveiro JMM,
Ueda T, Tamura T, Matsunaga N, Nakao T, Koyanagi S, Ohdo S, Yamaguchi Y, Hamachi I,
Ono M, Ojida A (2019) Selective and reversible modification of kinase cysteines with
chlorofluoroacetamides. Nat Chem Biol 15:250. https://doi.org/10.1038/s41589-018-0204-3
32. Zhang J, Yang PL, Gray NS (2009) Targeting cancer with small molecule kinase inhibitors.
Nat Rev Cancer 9:28–39. https://doi.org/10.1038/nrc2559
33. Traxler P (1998) Tyrosine kinase inhibitors in cancer treatment (part II). Expert Opin Ther Pat
8:1599–1625. https://doi.org/10.1517/13543776.8.12.1599
34. Traxler P, Furet P (1999) Strategies toward the design of novel and selective protein tyrosine
kinase inhibitors. Pharmacol Ther 82:195–206. https://doi.org/10.1016/S0163-7258(98)
00044-8
35. Backes A, Zech B, Felber B, Klebl B, Müller G (2008) Small-molecule inhibitors binding to
protein kinase. Part II: the novel pharmacophore approach of type II and type III inhibition.
Exp Opin Drug Discovery 3:1427–1449. https://doi.org/10.1517/17460440802580106
36. Liao JJ-L (2007) Molecular recognition of protein kinase binding pockets for design of potent
and selective kinase inhibitors. J Med Chem 50:409–424. https://doi.org/10.1021/jm0608107
37. Yoshida T, Kakizuka A, Imamura H (2016) BTeam, a novel BRET-based biosensor for the
accurate quantification of ATP concentration within living cells. Sci Rep 6:39618. https://doi.
org/10.1038/srep39618
38. Yen-Pon E, Li B, Acebrón-Garcia-de-Eulate M, Tomkiewicz-Raulet C, Dawson J, Lietha D,
Frame MC, Coumoul X, Garbay C, Etheve-Quelquejeu M, Chen H (2018) Structure-based
design, synthesis, and characterization of the first irreversible inhibitor of focal adhesion
kinase. ACS Chem Biol 13:2067–2073. https://doi.org/10.1021/acschembio.8b00250
39. Ferguson FM, Gray NS (2018) Kinase inhibitors: the road ahead. Nat Rev Drug Discov
17:353–377. https://doi.org/10.1038/nrd.2018.21
40. Zhao Z, Bourne PE (2018) Progress with covalent small-molecule kinase inhibitors. Drug
Discov Today 23:727–735. https://doi.org/10.1016/j.drudis.2018.01.035
41. Gilbert AM (2014) Recent advances in irreversible kinase inhibitors. Pharm Patent Anal
3:375–386. https://doi.org/10.4155/ppa.14.24
42. Sanderson K (2013) Irreversible kinase inhibitors gain traction. Nat Rev Drug Discov
12:649–651. https://doi.org/10.1038/nrd4103
43. Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, Flowers ME, Logan AC,
Nakamura R, Blazar BR, Li Y, Chang S, Lal I, Dubovsky J, James DF, Styles L, Jaglowski S
(2017) Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood
130:2243–2250. https://doi.org/10.1182/blood-2017-07-793786
44. Soria J-C, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH,
Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC,
Cheng Y, Cho EK, Voon PJ, Planchard D, Su W-C, Gray JE, Lee S-M, Hodge R,
86
M. Gehringer