4. Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252.
https://doi.org/10.1016/S0092-8674(00)00116-1
5. Hess J, Angel P, Schorpp-Kistner M (2004) AP-1 subunits: quarrel and harmony among
siblings. J Cell Sci 117:5965–5973. https://doi.org/10.1242/jcs.01589
6. Mehan S, Meena H, Sharma D, Sankhla R (2011) JNK: a stress-activated protein kinase
therapeutic strategies and involvement in Alzheimer’s and various neurodegenerative
abnormalities. J Mol Neurosci 43:376–390. https://doi.org/10.1007/s12031-010-9454-6
7. Resnick L, Fennell M (2004) Targeting JNK3 for the treatment of neurodegenerative disorders.
Drug Discov Today 9:932–939. https://doi.org/10.1016/S1359-6446(04)03251-9
8. Manning AM, Davis RJ (2003) Targeting JNK for therapeutic benefit: from JuNK to gold?
Nat Rev Drug Discov 2:554–565. https://doi.org/10.1038/nrd1132
9. 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
10. Gehringer M, Muth F, Koch P, Laufer SA (2015) c-Jun N-terminal kinase inhibitors: a patent
review (2010–2014). Expert Opin Ther Pat 25:849–872. https://doi.org/10.1517/13543776.
2015.1039984
11. Barkdull GC, Hondarrague Y, Meyer T, Harris JP, Keithley EM (2007) AM-111 reduces
hearing loss in a Guinea pig model of acute labyrinthitis. Laryngoscope 117:2174–2182.
https://doi.org/10.1097/MLG.0b013e3181461f92
12. Coleman JKM, Littlesunday C, Jackson R, Meyer T (2007) AM-111 protects against permanent
hearing loss from impulse noise trauma. Hearing Res 226:70–78. https://doi.org/10.1016/j.
heares.2006.05.006
13. Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu WM, Leisten JC, Motiwala A,
Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW (2001) SP600125, an
anthrapyrazolone inhibitor of Jun N-terminal kinase. P Natl Acad Sci USA 98:13681–13686.
https://doi.org/10.1073/pnas.251194298
14. Fabian MA, Biggs WH, Treiber DK, Atteridge CE, Azimioara MD, Benedetti MG, Carter TA,
Ciceri P, Edeen PT, Floyd M, Ford JM, Galvin M, Gerlach JL, Grotzfeld RM, Herrgard S,
Insko DE, Insko MA, Lai AG, Lelias JM, Mehta SA, Milanov ZV, Velasco AM, Wodicka LM,
Patel HK, Zarrinkar PP, Lockhart DJ (2005) A small molecule-kinase interaction map
for clinical kinase inhibitors. Nat Biotechnol 23:329–336. https://doi.org/10.1038/nbt1068
15. Heo Y-S, Kim SK, Seo CI, Kim YK, Sung B-J, Lee HS, Lee JI, Park S-Y, Kim JH, Hwang KY,
Hyun Y-L, Jeon YH, Ro S, Cho JM, Lee TG, Yang C-H (2004) Structural basis for the
selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125. EMBO J
23:2185–2195. https://doi.org/10.1038/sj.emboj.7600212
16. Goettert M, Luik S, Graeser R, Laufer SA (2011) A direct ELISA assay for quantitative
determination of the inhibitory potency of small molecules inhibitors for JNK3. J Pharm
Biomed Anal 55:236–240. https://doi.org/10.1016/j.jpba.2011.01.014
17. Feng YB, Chambers JW, Iqbal S, Koenig M, Park H, Cherry L, Hernandez P,
Figuera-Losada M, LoGrasso PV (2013) A small molecule bidentate-binding dual inhibitor
probe of the LRRK2 and JNK kinases. ACS Chem Biol 8:1747–1754. https://doi.org/10.1021/
cb3006165
18. Zhang T, Inesta-Vaquera F, Niepel M, Zhang JM, 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
19. Alam M, Beevers RE, Ceska T, Davenport RJ, Dickson KM, Fortunato M, Gowers L,
Haughan AF, James LA, Jones MW, Kinsella N, Lowe C, Meissner JWG, Nicolas AL,
Perry BG, Phillips DJ, Pitt WR, Platt A, Ratcliffe AJ, Sharpe A, Tait LJ (2007) Synthesis
and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors. Bioorg Med
Chem Lett 17:3463–3467. https://doi.org/10.1016/j.bmcl.2009.03.023
222
P. Koch
https://doi.org/10.1016/S0092-8674(00)00116-1
5. Hess J, Angel P, Schorpp-Kistner M (2004) AP-1 subunits: quarrel and harmony among
siblings. J Cell Sci 117:5965–5973. https://doi.org/10.1242/jcs.01589
6. Mehan S, Meena H, Sharma D, Sankhla R (2011) JNK: a stress-activated protein kinase
therapeutic strategies and involvement in Alzheimer’s and various neurodegenerative
abnormalities. J Mol Neurosci 43:376–390. https://doi.org/10.1007/s12031-010-9454-6
7. Resnick L, Fennell M (2004) Targeting JNK3 for the treatment of neurodegenerative disorders.
Drug Discov Today 9:932–939. https://doi.org/10.1016/S1359-6446(04)03251-9
8. Manning AM, Davis RJ (2003) Targeting JNK for therapeutic benefit: from JuNK to gold?
Nat Rev Drug Discov 2:554–565. https://doi.org/10.1038/nrd1132
9. 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
10. Gehringer M, Muth F, Koch P, Laufer SA (2015) c-Jun N-terminal kinase inhibitors: a patent
review (2010–2014). Expert Opin Ther Pat 25:849–872. https://doi.org/10.1517/13543776.
2015.1039984
11. Barkdull GC, Hondarrague Y, Meyer T, Harris JP, Keithley EM (2007) AM-111 reduces
hearing loss in a Guinea pig model of acute labyrinthitis. Laryngoscope 117:2174–2182.
https://doi.org/10.1097/MLG.0b013e3181461f92
12. Coleman JKM, Littlesunday C, Jackson R, Meyer T (2007) AM-111 protects against permanent
hearing loss from impulse noise trauma. Hearing Res 226:70–78. https://doi.org/10.1016/j.
heares.2006.05.006
13. Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu WM, Leisten JC, Motiwala A,
Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW (2001) SP600125, an
anthrapyrazolone inhibitor of Jun N-terminal kinase. P Natl Acad Sci USA 98:13681–13686.
https://doi.org/10.1073/pnas.251194298
14. Fabian MA, Biggs WH, Treiber DK, Atteridge CE, Azimioara MD, Benedetti MG, Carter TA,
Ciceri P, Edeen PT, Floyd M, Ford JM, Galvin M, Gerlach JL, Grotzfeld RM, Herrgard S,
Insko DE, Insko MA, Lai AG, Lelias JM, Mehta SA, Milanov ZV, Velasco AM, Wodicka LM,
Patel HK, Zarrinkar PP, Lockhart DJ (2005) A small molecule-kinase interaction map
for clinical kinase inhibitors. Nat Biotechnol 23:329–336. https://doi.org/10.1038/nbt1068
15. Heo Y-S, Kim SK, Seo CI, Kim YK, Sung B-J, Lee HS, Lee JI, Park S-Y, Kim JH, Hwang KY,
Hyun Y-L, Jeon YH, Ro S, Cho JM, Lee TG, Yang C-H (2004) Structural basis for the
selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125. EMBO J
23:2185–2195. https://doi.org/10.1038/sj.emboj.7600212
16. Goettert M, Luik S, Graeser R, Laufer SA (2011) A direct ELISA assay for quantitative
determination of the inhibitory potency of small molecules inhibitors for JNK3. J Pharm
Biomed Anal 55:236–240. https://doi.org/10.1016/j.jpba.2011.01.014
17. Feng YB, Chambers JW, Iqbal S, Koenig M, Park H, Cherry L, Hernandez P,
Figuera-Losada M, LoGrasso PV (2013) A small molecule bidentate-binding dual inhibitor
probe of the LRRK2 and JNK kinases. ACS Chem Biol 8:1747–1754. https://doi.org/10.1021/
cb3006165
18. Zhang T, Inesta-Vaquera F, Niepel M, Zhang JM, 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
19. Alam M, Beevers RE, Ceska T, Davenport RJ, Dickson KM, Fortunato M, Gowers L,
Haughan AF, James LA, Jones MW, Kinsella N, Lowe C, Meissner JWG, Nicolas AL,
Perry BG, Phillips DJ, Pitt WR, Platt A, Ratcliffe AJ, Sharpe A, Tait LJ (2007) Synthesis
and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors. Bioorg Med
Chem Lett 17:3463–3467. https://doi.org/10.1016/j.bmcl.2009.03.023
222
P. Koch