Design and characterization of a potent and selective dual ATP- and substrate-competitive subnanomolar bidentate c-Jun N-terminal kinase (JNK) inhibitor

Journal of Medicinal Chemistry

Volumn 54, Issue 18, 2011, Pages 6206-6214

  Stebbins, John L ^a   De, Surya K ^a   Pavlickova, Petra ^a   Chen, Vida ^a   MacHleidt, Thomas ^b   Chen, Li Hsing ^a   Kuntzen, Christian ^c   Kitada, Shinichi ^a   Karin, Michael ^c   Pellecchia, Maurizio ^a  

^a BURNHAM INSTITUTE   (United States)

^b Life Technologies   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; ADENOSINE TRIPHOSPHATE; GLUCOSE; SCAFFOLD PROTEIN; STRESS ACTIVATED PROTEIN KINASE; STRESS ACTIVATED PROTEIN KINASE INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DATA ANALYSIS; DIABETES MELLITUS; DRUG DESIGN; ENZYME ACTIVITY; FEMALE; GLUCOSE TOLERANCE; HUMAN; HUMAN CELL; IC 50; IN VIVO STUDY; LIVER INJURY; MOUSE; NONHUMAN;

ADENOSINE TRIPHOSPHATE; AMINO ACID MOTIFS; ANIMALS; BINDING, COMPETITIVE; CELL LINE; CONSENSUS SEQUENCE; CYTOKINES; DIABETES MELLITUS, TYPE 2; DRUG DESIGN; DRUG-INDUCED LIVER INJURY; FEMALE; GLUCOSE INTOLERANCE; HUMANS; HYPOGLYCEMIC AGENTS; JNK MITOGEN-ACTIVATED PROTEIN KINASES; MACROPHAGES; MALE; MICE; MICE, INBRED C57BL; MODELS, MOLECULAR; MOLECULAR MIMICRY; PEPTIDES; PHOSPHORYLATION; PROTEIN BINDING; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 80052815074     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200479c     Document Type: Article

References (50)

1. Bogoyevitch, M. A. Therapeutic promise of JNK ATP-noncompetitive inhibitors Trends Mol. Med. 2005, 11, 232-239 (Pubitemid 40692313)
2. Gupta, S.; Barrett, T.; Whitmarsh, A. J.; Cavanagh, J.; Sluss, H. K.; Derijard, B.; Davis, R. J. Selective interaction of JNK protein kinase isoforms with transcription factors EMBO J. 1996, 15, 2760-2770 (Pubitemid 26176253)
3. Manning, A. M.; Davis, R. J. Targeting JNK for therapeutic benefit: from junk to gold? Nature Rev. Drug Discovery 2003, 2, 554-565 (Pubitemid 37361747)
4. Martin, J. H.; Mohit, A. A.; Miller, C. A. Developmental expression in the mouse nervous system of the p493F12 SAP kinase Brain Res. Mol. Brain Res. 1996, 35, 47-57
5. Ip, Y. T.; Davis, R. J. Signal transduction by the c-Jun N-terminal kinase (JNK)-from inflammation to development Curr. Opin. Cell Biol. 1998, 10, 205-219 (Pubitemid 28174763)
6. Leppa, S.; Bohmann, D. Diverse functions of JNK signaling and c-Jun in stress response and apoptosis Oncogene 1999, 18, 6158-6162
7. Minden, A.; Karin, M. Regulation and function of the JNK subgroup of MAP kinases Biochim. Biophys. Acta 1997, 1333, F85-104
8. Solinas, G.; Karin, M. JNK1 and IKK{beta}: molecular links between obesity and metabolic dysfunction FASEB J. 2010, 24, 2596-2611
9. Bogoyevitch, M. A.; Ngoei, K. R.; Zhao, T. T.; Yeap, Y. Y.; Ng, D. C. c-Jun N-terminal kinase (JNK) signaling: recent advances and challenges Biochim. Biophys. Acta 2010, 1804, 463-475
10. Bogoyevitch, M. A.; Kobe, B. Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases Microbiol. Mol. Biol. Rev. 2006, 70, 1061-1095 (Pubitemid 44958264)
11. Heo, Y. S.; Kim, S. K.; Seo, C. I.; Kim, Y. K.; Sung, B. J.; Lee, H. S.; Lee, J. I.; Park, S. Y.; Kim, J. H.; Hwang, K. Y.; Hyun, Y. L.; Jeon, Y. H.; Ro, S.; Cho, J. M.; Lee, T. G.; Yang, C. H. Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125 EMBO J. 2004, 23, 2185-2195 (Pubitemid 38833228)
12. Dickens, M.; Rogers, J. S.; Cavanagh, J.; Raitano, A.; Xia, Z.; Halpern, J. R.; Greenberg, M. E.; Sawyers, C. L.; Davis, R. J. A cytoplasmic inhibitor of the JNK signal transduction pathway Science 1997, 277, 693-696 (Pubitemid 27373916)
13. Barr, R. K.; Kendrick, T. S.; Bogoyevitch, M. A. Identification of the critical features of a small peptide inhibitor of JNK activity J. Biol. Chem. 2002, 277, 10987-10997 (Pubitemid 34952855)
14. Ho, D. T.; Bardwell, A. J.; Abdollahi, M.; Bardwell, L. A docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates J. Biol. Chem. 2003, 278, 32662-32672 (Pubitemid 37055705)
15. Borsello, T.; Clarke, P. G.; Hirt, L.; Vercelli, A.; Repici, M.; Schorderet, D. F.; Bogousslavsky, J.; Bonny, C. A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia Nature Med. 2003, 9, 1180-1186 (Pubitemid 37173703)
16. Bonny, C.; Oberson, A.; Negri, S.; Sauser, C.; Schorderet, D. F. Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death Diabetes 2001, 50, 77-82 (Pubitemid 32047984)
17. Kim, J. A.; Lee, J.; Margolis, R. L.; Fotedar, R. SP600125 suppresses Cdk1 and induces endoreplication directly from G2 phase, independent of JNK inhibition Oncogene 2010, 29, 1702-1716
18. Bain, J.; McLauchlan, H.; Elliott, M.; Cohen, P. The specificities of protein kinase inhibitors: an update Biochem. J. 2003, 371, 199-204 (Pubitemid 36458094)
19. Bain, J.; Plater, L.; Elliott, M.; Shpiro, N.; Hastie, C. J.; McLauchlan, H.; Klevernic, I.; Arthur, J. S.; Alessi, D. R.; Cohen, P. The selectivity of protein kinase inhibitors: a further update Biochem. J. 2007, 408, 297-315
20. Siddiqui, M. A.; Reddy, P. A. Small molecule JNK (c-Jun N-terminal kinase) inhibitors J. Med. Chem. 2010, 53, 3005-3012
21. Vazquez, J.; De, S. K.; Chen, L. H.; Riel-Mehan, M.; Emdadi, A.; Cellitti, J.; Stebbins, J. L.; Rega, M. F.; Pellecchia, M. Development of Paramagnetic Probes for Molecular Recognition Studies in Protein Kinases J. Med. Chem. 2008, 51, 3460-3465 (Pubitemid 351875002)
22. Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Discovering high-affinity ligands for proteins: SAR by NMR Science 1996, 274, 1531-1534 (Pubitemid 26403929)
23. Jahnke, W.; Blommers, M. J.; Fernandez, C.; Zwingelstein, C.; Amstutz, R. Strategies for the NMR-based identification and optimization of allosteric protein kinase inhibitors ChemBioChem 2005, 6, 1607-1610 (Pubitemid 41296967)
24. Murray, B. W.; Bennett, B. L.; Sasaki, D. T. Analysis of pharmacologic inhibitors of Jun N-terminal kinases Methods Enzymol. 2001, 332, 432-452 (Pubitemid 32275400)
25. Enkvist, E.; Lavogina, D.; Raidaru, G.; Vaasa, A.; Viil, I.; Lust, M.; Viht, K.; Uri, A. Conjugation of adenosine and hexa-(d -arginine) leads to a nanomolar bisubstrate-analog inhibitor of basophilic protein kinases J. Med. Chem. 2006, 49, 7150-7159 (Pubitemid 44886000)
26. Hill, Z. B.; Perera, B. G.; Maly, D. J. A chemical genetic method for generating bivalent inhibitors of protein kinases J. Am. Chem. Soc. 2009, 131, 6686-6688
27. Lavogina, D.; Enkvist, E.; Uri, A. Bisubstrate inhibitors of protein kinases: from principle to practical applications ChemMedChem 2010, 5, 23-34
28. Lee, J. H.; Kumar, S.; Lawrence, D. S. Stepwise combinatorial evolution of Akt bisubstrate inhibitors ChemBioChem 2008, 9, 507-509
29. Pflug, A.; Rogozina, J.; Lavogina, D.; Enkvist, E.; Uri, A.; Engh, R. A.; Bossemeyer, D. Diversity of bisubstrate binding modes of adenosine analogue-oligoarginine conjugates in protein kinase a and implications for protein substrate interactions J. Mol. Biol. 2010, 403, 66-77
30. Fischer, P. M. The design, synthesis and application of stereochemical and directional peptide isomers: a critical review Curr. Protein Pept. Sci. 2003, 4, 339-356 (Pubitemid 37236348)
31. Shah, M.; Stebbins, J. L.; Dewing, A.; Qi, J.; Pellecchia, M.; Ronai, Z. A. Inhibition of Siah2 ubiquitin ligase by vitamin K3 (menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis Pigm. Cell Melanoma Res. 2009, 22, 799-808
32. Davies, S. P.; Reddy, H.; Caivano, M.; Cohen, P. Specificity and mechanism of action of some commonly used protein kinase inhibitors Biochem. J. 2000, 351, 95-105
33. Robers, M. B.; Horton, R. A.; Bercher, M. R.; Vogel, K. W.; Machleidt, T. High-throughput cellular assays for regulated posttranslational modifications Anal. Biochem. 2008, 372, 189-197 (Pubitemid 350116771)
34. Comalada, M.; Xaus, J.; Valledor, A. F.; Lopez-Lopez, C.; Pennington, D. J.; Celada, A. PKC epsilon is involved in JNK activation that mediates LPS-induced TNF-alpha, which induces apoptosis in macrophages Am. J. Physiol. Cell Physiol. 2003, 285, C1235-C1245
35. Baldassare, J. J.; Bi, Y.; Bellone, C. J. The role of p38 mitogen-activated protein kinase in IL-1 beta transcription J. Immunol. 1999, 162, 5367-5373 (Pubitemid 29307144)
36. Solinas, G.; Vilcu, C.; Neels, J. G.; Bandyopadhyay, G. K.; Luo, J. L.; Naugler, W.; Grivennikov, S.; Wynshaw-Boris, A.; Scadeng, M.; Olefsky, J. M.; Karin, M. JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity Cell Metab. 2007, 6, 386-397 (Pubitemid 350012000)
37. Cho, Y. R.; Kim, H. J.; Park, S. Y.; Ko, H. J.; Hong, E. G.; Higashimori, T.; Zhang, Z.; Jung, D. Y.; Ola, M. S.; Lanoue, K. F.; Leiter, E. H.; Kim, J. K. Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes Am. J. Physiol. Endocrinol. Metab. 2007, 293, E327-336
38. Kaoud, T. S.; Mitra, S.; Lee, S.; Taliaferro, J.; Cantrell, M.; Linse, K. D.; Van Den Berg, C. L.; Dalby, K. N. Development of JNK2-Selective Peptide Inhibitors That Inhibit Breast Cancer Cell Migration ACS Chem. Biol. 2011, 6, 658-666
39. Maeda, S.; Chang, L.; Li, Z. W.; Luo, J. L.; Leffert, H.; Karin, M. IKKbeta is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFalpha Immunity 2003, 19, 725-737 (Pubitemid 37490797)
40. Wang, Y.; Singh, R.; Lefkowitch, J. H.; Rigoli, R. M.; Czaja, M. J. Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway J. Biol. Chem. 2006, 281, 15258-15267 (Pubitemid 43855115)
41. Malhi, H.; Gores, G. J. Cellular and molecular mechanisms of liver injury Gastroenterology 2008, 134, 1641-1654 (Pubitemid 351615416)
42. Stebbins, J. L.; De, S. K.; Machleidt, T.; Becattini, B.; Vazquez, J.; Kuntzen, C.; Chen, L. H.; Cellitti, J. F.; Riel-Mehan, M.; Emdadi, A.; Solinas, G.; Karin, M.; Pellecchia, M. Identification of a new JNK inhibitor targeting the JNK-JIP interaction site Proc. Natl. Acad. Sci. U.S.A 2008, 105, 16809-16813
43. De, S. K.; Chen, V.; Stebbins, J. L.; Chen, L. H.; Cellitti, J. F.; Machleidt, T.; Barile, E.; Riel-Mehan, M.; Dahl, R.; Yang, L.; Emdadi, A.; Murphy, R.; Pellecchia, M. Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors Bioorg. Med. Chem. 2010, 18, 590-596
44. De, S. K.; Chen, L. H.; Stebbins, J. L.; Machleidt, T.; Riel-Mehan, M.; Dahl, R.; Chen, V.; Yuan, H.; Barile, E.; Emdadi, A.; Murphy, R.; Pellecchia, M. Discovery of 2-(5-nitrothiazol-2-ylthio)benzo[ d ]thiazoles as novel c-Jun N-terminal kinase inhibitors Bioorg. Med. Chem. 2009, 17, 2712-2717
45. De, S. K.; Stebbins, J. L.; Chen, L. H.; Riel-Mehan, M.; Machleidt, T.; Dahl, R.; Yuan, H.; Emdadi, A.; Barile, E.; Chen, V.; Murphy, R.; Pellecchia, M. Design, synthesis, and structure-activity relationship of substrate competitive, selective, and in vivo active triazole and thiadiazole inhibitors of the c-Jun N-terminal kinase J. Med. Chem. 2009, 52, 1943-1952
46. Caelles, C.; Morales, M. Assays to measure stress-activated MAPK activity Methods Mol. Biol. 2004, 282, 145-156
47. Huwiler, K. G.; Machleidt, T.; Chase, L.; Hanson, B.; Robers, M. B. Characterization of serotonin 5-hydroxytryptamine-1A receptor activation using a phospho-extracellular-signal regulated kinase 2 sensor Anal. Biochem. 2009, 393, 95-104
48. Eldridge, M. D.; Murray, C. W.; Auton, T. R.; Paolini, G. V.; Mee, R. P. Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes J. Comput.-Aided Mol. Des. 1997, 11, 425-445 (Pubitemid 127505895)
49. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking J. Mol. Biol. 1997, 267, 727-748 (Pubitemid 27170693)
50. Teschner, M.; Henn, C.; Vollhardt, H.; Reiling, S.; Brickmann, J. Texture mapping: a new tool for molecular graphics J. Mol. Graphics 1994, 12, 98-105 (Pubitemid 24219249)