Small-molecule inhibitors of cytokine-mediated STAT1 signal transduction in β-cells with improved aqueous solubility

Journal of Medicinal Chemistry

Volumn 56, Issue 10, 2013, Pages 4125-4129

  Scully, Stephen S ^a   Tang, Alicia J ^a   Lundh, Morten ^a,b   Mosher, Carrie M ^a   Perkins, Kedar M ^a   Wagner, Bridget K ^a  

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

BRD 0476; CYTOKINE; GAMMA INTERFERON; NAPHTHYL GROUP; QUINOLINE DERIVATIVE; STAT1 PROTEIN; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ANIMAL CELL; APOPTOSIS; AQUEOUS SOLUTION; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG INHIBITION; DRUG MECHANISM; DRUG SOLUBILITY; DRUG SYNTHESIS; IC 50; MEDIATOR; NONHUMAN; PANCREAS ISLET BETA CELL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION;

ANILINE COMPOUNDS; APOPTOSIS; BLOTTING, WESTERN; CASPASE 3; CASPASE 7; CELL LINE; CHEMISTRY, PHARMACEUTICAL; CYTOKINES; HUMANS; INDICATORS AND REAGENTS; INSULIN-SECRETING CELLS; INTERFERON-GAMMA; PHOSPHORYLATION; SIGNAL TRANSDUCTION; SOLUBILITY; STAT1 TRANSCRIPTION FACTOR; STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS; UREA;

EID: 84878104619     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400397x     Document Type: Article

References (23)

1. IDF Diabetes Atlas, 5th ed.; International Diabetes Federation: Brussels, 2011; http://www.idf.org/diabetesatlas.
2. Grunnet, L. G.; Aikin, R.; Tonnesen, M. F.; Paraskevas, S.; Blaabjerg, L.; Størling, J.; Rosenberg, L.; Billestrup, N.; Maysinger, D.; Mandrup-Poulsen, T. Pro-inflammatory cytokines activate the intrinsic apoptotic pathway in β-cells Diabetes 2009, 58, 1807-1815
3. Matsuda, T.; Ferreri, K.; Todorov, I.; Kuroda, Y.; Smith, C. V.; Kandeel, F.; Mullen, Y. Silymarin protects pancreatic β-cells against cytokine-mediated toxicity: implication of c-Jun NH2-terminal kinase and janus kinase/signal transducer and activator of transcription pathways Endocrinology 2005, 146, 175-185
4. Kim, E. K.; Kwon, K. B.; Song, M. Y.; Han, M. J.; Lee, J. H.; Lee, Y. R.; Ryu, D. G.; Park, B. H.; Park, J. W. Flavonoids protect against cytokine-induced pancreatic β-cell damage through suppression of nuclear factor kappaB activation Pancreas 2007, 35, e1-e9
5. Larsen, L.; Tonnesen, M.; Ronn, S. G.; Storling, J.; Jorgensen, S.; Mascagni, P.; Dinarello, C. A.; Billestrup, N.; Mandrup-Poulsen, T. Inhibition of histone deacetylases prevents cytokine-induced toxicity in β-cells Diabetologia 2007, 50, 779-789
6. Chou, D. H-C.; Holson, E. B.; Wagner, F. F.; Tang, A. J.; Maglathlin, R. L.; Lewis, T. A.; Schreiber, S. L.; Wagner, B. K. Chem. Biol. 2012, 19, 669-673
7. Chou, D. H-C.; Bodycombe, N. E.; Carrinski, H. A.; Lewis, T. A.; Clemons, P. A.; Schreiber, S. L.; Wagner, B. K. Small-molecule suppressors of cytokine-induced β-cell apoptosis ACS Chem. Biol. 2010, 5, 729-734
8. Schreiber, S. L. Target-oriented and diversity-oriented organic synthesis in drug discovery Science 2000, 287, 1964-1969
9. Burke, M. D.; Schreiber, S. L. A planning strategy for diversity-oriented synthesis Angew. Chem., Int. Ed. 2004, 43, 46-58
10. Nielsen, T. E.; Schreiber, S. L. Towards the optimal screening collection: a synthesis strategy Angew. Chem., Int. Ed. 2008, 47, 48-56
11. Chou, D. H-C.; Duvall, J. R.; Gerard, B.; Liu, H.; Pandya, B. A.; Suh, B.-C.; Forbeck, E. M.; Faloon, P.; Wagner, B. K.; Marcaurelle, L. A. Synthesis of a novel suppressor of β-cell apoptosis via diversity-oriented synthesis ACS Med. Chem. Lett. 2011, 2, 698-702
12. Marcaurelle, L. A.; Comer, E.; Dandapani, S.; Duvall, J. R.; Gerard, B.; Kesavan, S.; Lee, M. D.; Liu, H.; Lowe, J. T.; Marie, J.-C.; Mulrooney, C. A.; Pandya, B. A.; Rowley, A.; Ryba, T. D.; Suh, B.-C.; Wei, J.; Young, D. W.; Akella, L. B.; Ross, N. T.; Zhang, Y.-L.; Fass, D. M.; Reis, S. A.; Zhao, W.-N.; Haggarty, S. J.; Palmer, M.; Foley, M. A. An aldol-based build/couple/pair strategy for the synthesis of medium- and large-sized rings: discovery of macrocyclic histone deacetylase inhibitors J. Am. Chem. Soc. 2010, 132, 16962-16976
13. Gerard, B.; Duvall, J. R.; Lowe, J. T.; Murillo, T.; Wei, J.; Akella, L. B.; Marcaurelle, L. A. Synthesis of a stereochemically diverse library of medium-sized lactam and sultams via S(N)Ar cycloetherification ACS Comb. Sci. 2011, 13, 365-374
14. Sigurdsson, S. T.; Seeger, B.; Kutzke, U.; Eckstein, F. A mild and simple method for the preparation of isocyanates from aliphatic amines using trichloromethyl chloroformate. Synthesis of an isocyanate containing an activated double disulfide J. Org. Chem. 1996, 61, 3883-3884
15. Merglen, A.; Theander, S.; Rubi, B.; Chaffard, G.; Wollheim, C. B.; Maechler, P. Glucose sensitivity and metabolism-secretion coupling studied during two-year continuous culture in INS-1E insulinoma cells Endocrinology 2003, 145, 667-668
16. Ishikawa, M.; Hashimoto, Y. Improvement in aqueous solubility in small molecule drug discovery programs by disruption of molecular planarity and symmetry J. Med. Chem. 2011, 54, 1539-1554
17. Guzman-Perez, A.; Wester, R. T.; Allen, M. C.; Brown, J. A.; Buchholz, A. R.; Cook, E. R.; Day, W. W.; Hamanaka, E. S.; Kennedy, S. P.; Knight, D. R.; Kowalczyk, P. J.; Marala, R. B.; Mularski, C. J.; Novomisle, W. A.; Ruggeri, R. B.; Tracey, W. R.; Hill, R. J. Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility Bioorg. Med. Chem. Lett. 2001, 11, 803-807
18. Pérez-Melero, C.; Maya, A. B. S.; del Rey, B.; Peláez, R.; Caballero, E.; Medarde, M. A new family of quinoline and quinoxaline analogous of combrestatins Bioorg. Med. Chem. Lett. 2004, 14, 3771-3774
19. Shuai, K.; Liu, B. Regulation of JAK-STAT signalling in the immune system Nature Rev. Immunol. 2003, 3, 900-911
20. Schindler, C. S.; Levy, D. E.; Decker, T. JAK-STAT signaling: from interferons to cytokines J. Biol. Chem. 2007, 282, 20059-20063
21. Moore, F.; Naamane, N.; Colli, M. L.; Bouckenooghe, T.; Ortis, F.; Gurzov, E. N.; Igoillo-Esteve, M.; Mathieu, C.; Bontempi, G.; Thykjaer, T.; Ørntoft, T. F.; Eizirik, D. L. STAT1 is a master regulator of pancreatic β-cell apoptosis and islet inflammation J. Biol. Chem. 2011, 286, 929-941
22. Klampfer, L.; Huang, J.; Sasazuki, T.; Shirasawa, S.; Augenlicht, L. Inhibition of interferon γ signaling by the short chain fatty acid butyrate Mol. Cancer Res. 2003, 1, 855-862
23. Klampfer, L.; Huang, J.; Swaby, L.-A.; Augenlicht, L. Requirement of histone deacetylase activity for signaling by STAT1 J. Biol. Chem. 2004, 279, 30358-30368