Peck B, Davis AB, Bettoun D (2011) Discovery of novel Cyanamide-based inhibitors of
Cathepsin C. ACS Med Chem Lett 2:142–147. https://doi.org/10.1021/ml100212k
84. Zapf CW, Gerstenberger BS, Xing L, Limburg DC, Anderson DR, Caspers N, Han S,
Aulabaugh A, Kurumbail R, Shakya S, Li X, Spaulding V, Czerwinski RM, Seth N, Medley
QG (2012) Covalent inhibitors of interleukin-2 inducible T cell kinase (Itk) with nanomolar
potency in a whole-blood assay. J Med Chem 55:10047–10063. https://doi.org/10.1021/
jm301190s
85. Harling JD, Deakin AM, Campos S, Grimley R, Chaudry L, Nye C, Polyakova O, Bessant
CM, Barton N, Somers D, Barrett J, Graves RH, Hanns L, Kerr WJ, Solari R (2013) Discovery
of novel irreversible inhibitors of interleukin (IL)-2-inducible tyrosine kinase (Itk) by targeting
cysteine 442 in the ATP pocket. J Biol Chem 288:28195–28206. https://doi.org/10.1074/jbc.
M113.474114
86. Forster M, Gehringer M, Laufer SA (2017) Recent advances in JAK3 inhibition: isoform
selectivity by covalent cysteine targeting. Bioorg Med Chem Lett 27:4229–4237. https://doi.
org/10.1016/j.bmcl.2017.07.079
87. 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
88. 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
89. Liu F, Zhang X, Weisberg E, Chen S, Hur W, Wu H, Zhao Z, Wang W, Mao M, Cai C, Simon
NI, Sanda T, Wang J, Look AT, Griffin JD, Balk SP, Liu Q, Gray NS (2013) Discovery of a
selective irreversible BMX inhibitor for prostate cancer. ACS Chem Biol 8:1423–1428.
https://doi.org/10.1021/cb4000629
90. Liang X, Lv F, Wang B, Yu K, Wu H, Qi Z, Jiang Z, Chen C, Wang A, Miao W, Wang W,
Hu Z, Liu J, Liu X, Zhao Z, Wang L, Zhang S, Ye Z, Wang C, Ren T, Wang Y, Liu Q, Liu J
(2017) Discovery of 2-((3-Acrylamido-4-methylphenyl)amino)-N-(2-methyl-5-(3,4,5trimethoxybenzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-BMX078) as a highly potent and selective type II irreversible bone marrow kinase in the X
Chromosome (BMX) kinase inhibitor. J Med Chem 60:1793–1816. https://doi.org/10.1021/
acs.jmedchem.6b01413
91. 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
92. Shraga A, Olshvang E, Davidzohn N, Khoshkenar P, Germain N, Shurrush K, Carvalho S,
Avram L, Albeck S, Unger T, Lefker B, Subramanyam C, Hudkins RL, Mitchell A,
Shulman Z, Kinoshita T, London N (2018) Covalent docking identifies a potent and selective
MKK7 inhibitor. Cell Chem Biol. https://doi.org/10.1016/j.chembiol.2018.10.011
93. Wolle P, Hardick J, Cronin SJF, Engel J, Baumann M, Lategahn J, Penninger JM, Rauh D
(2019) Targeting the MKK7–JNK (mitogen-activated protein kinase kinase 7–c-Jun
N-terminal kinase) pathway with covalent inhibitors. J Med Chem 62:2843–2848. https://
doi.org/10.1021/acs.jmedchem.9b00102
94. Erlanson DA, Arndt JW, Cancilla MT, Cao K, Elling RA, English N, Friedman J, Hansen SK,
Hession C, Joseph I, Kumaravel G, Lee W-C, Lind KE, McDowell RS, Miatkowski K,
Nguyen C, Nguyen TB, Park S, Pathan N, Penny DM, Romanowski MJ, Scott D, Silvian L,
Simmons RL, Tangonan BT, Yang W, Sun L (2011) Discovery of a potent and highly
selective PDK1 inhibitor via fragment-based drug discovery. Bioorg Med Chem Lett
21:3078–3083. https://doi.org/10.1016/j.bmcl.2011.03.032
90
M. Gehringer
Cathepsin C. ACS Med Chem Lett 2:142–147. https://doi.org/10.1021/ml100212k
84. Zapf CW, Gerstenberger BS, Xing L, Limburg DC, Anderson DR, Caspers N, Han S,
Aulabaugh A, Kurumbail R, Shakya S, Li X, Spaulding V, Czerwinski RM, Seth N, Medley
QG (2012) Covalent inhibitors of interleukin-2 inducible T cell kinase (Itk) with nanomolar
potency in a whole-blood assay. J Med Chem 55:10047–10063. https://doi.org/10.1021/
jm301190s
85. Harling JD, Deakin AM, Campos S, Grimley R, Chaudry L, Nye C, Polyakova O, Bessant
CM, Barton N, Somers D, Barrett J, Graves RH, Hanns L, Kerr WJ, Solari R (2013) Discovery
of novel irreversible inhibitors of interleukin (IL)-2-inducible tyrosine kinase (Itk) by targeting
cysteine 442 in the ATP pocket. J Biol Chem 288:28195–28206. https://doi.org/10.1074/jbc.
M113.474114
86. Forster M, Gehringer M, Laufer SA (2017) Recent advances in JAK3 inhibition: isoform
selectivity by covalent cysteine targeting. Bioorg Med Chem Lett 27:4229–4237. https://doi.
org/10.1016/j.bmcl.2017.07.079
87. 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
88. 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
89. Liu F, Zhang X, Weisberg E, Chen S, Hur W, Wu H, Zhao Z, Wang W, Mao M, Cai C, Simon
NI, Sanda T, Wang J, Look AT, Griffin JD, Balk SP, Liu Q, Gray NS (2013) Discovery of a
selective irreversible BMX inhibitor for prostate cancer. ACS Chem Biol 8:1423–1428.
https://doi.org/10.1021/cb4000629
90. Liang X, Lv F, Wang B, Yu K, Wu H, Qi Z, Jiang Z, Chen C, Wang A, Miao W, Wang W,
Hu Z, Liu J, Liu X, Zhao Z, Wang L, Zhang S, Ye Z, Wang C, Ren T, Wang Y, Liu Q, Liu J
(2017) Discovery of 2-((3-Acrylamido-4-methylphenyl)amino)-N-(2-methyl-5-(3,4,5trimethoxybenzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-BMX078) as a highly potent and selective type II irreversible bone marrow kinase in the X
Chromosome (BMX) kinase inhibitor. J Med Chem 60:1793–1816. https://doi.org/10.1021/
acs.jmedchem.6b01413
91. 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
92. Shraga A, Olshvang E, Davidzohn N, Khoshkenar P, Germain N, Shurrush K, Carvalho S,
Avram L, Albeck S, Unger T, Lefker B, Subramanyam C, Hudkins RL, Mitchell A,
Shulman Z, Kinoshita T, London N (2018) Covalent docking identifies a potent and selective
MKK7 inhibitor. Cell Chem Biol. https://doi.org/10.1016/j.chembiol.2018.10.011
93. Wolle P, Hardick J, Cronin SJF, Engel J, Baumann M, Lategahn J, Penninger JM, Rauh D
(2019) Targeting the MKK7–JNK (mitogen-activated protein kinase kinase 7–c-Jun
N-terminal kinase) pathway with covalent inhibitors. J Med Chem 62:2843–2848. https://
doi.org/10.1021/acs.jmedchem.9b00102
94. Erlanson DA, Arndt JW, Cancilla MT, Cao K, Elling RA, English N, Friedman J, Hansen SK,
Hession C, Joseph I, Kumaravel G, Lee W-C, Lind KE, McDowell RS, Miatkowski K,
Nguyen C, Nguyen TB, Park S, Pathan N, Penny DM, Romanowski MJ, Scott D, Silvian L,
Simmons RL, Tangonan BT, Yang W, Sun L (2011) Discovery of a potent and highly
selective PDK1 inhibitor via fragment-based drug discovery. Bioorg Med Chem Lett
21:3078–3083. https://doi.org/10.1016/j.bmcl.2011.03.032
90
M. Gehringer