Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded Library Technology (ELT)

ACS Medicinal Chemistry Letters

Volumn 6, Issue 8, 2015, Pages 888-893

  Ding, Yun ^a   O'Keefe, Heather ^a   DeLorey, Jennifer L ^b   Israel, David I ^a   Messer, Jeffrey A ^a   Chiu, Cynthia H ^a   Skinner, Steven R ^a   Matico, Rosalie E ^a   Murray Thompson, Monique F ^a   Li, Fan ^d   Clark, Matthew A ^c   Cuozzo, John W ^c   Arico Muendel, Christopher ^a   Morgan, Barry A ^e  

^a GLAXOSMITHKLINE   (United States)

^b Tedor Pharma Inc   (United States)

^c X Chem Incorporated   (United States)

^d Program on Opioid Risk Management   (United States)

^e BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

ADAMTS 4; DNA encoded library; inhibitors

Indexed keywords

AGGRECANASE 1; AGGRECANASE 2; COLLAGENASE 3; DNA; ENZYME INHIBITOR; TRIAZINE; VON WILLEBRAND FACTOR CLEAVING PROTEINASE;

ARTICLE; DNA LIBRARY; DRUG POTENCY; DRUG SYNTHESIS; IC50; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 84938931101     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/acsmedchemlett.5b00138     Document Type: Article

References (21)

1. Tortorella, M. D.; Malfait, A. M. Will the Real Aggrecanase(s) Step Up: Evaluating the Criteria That Define Aggrecanase Activity in Osteoarthritis Curr. Pharm. Biotechnol. 2008, 9, 16-23 10.2174/138920108783497622#sthash.Wj45IQRp.dpuf
2. Rienzo, F. D.; Saxena, P.; Filomia, F.; Caselli, C.; Colace, F.; Stasi, L.; Giordani, A.; Menziani, M. C. Progress Towards the Identification of New Aggrecanase Inhibitors Curr. Med. Chem. 2009, 16, 2395-2415 10.2174/092986709788682092
3. Malfait, A. M.; Liu, R. Q.; Ijiri, K.; Setsuro, K.; Tortorella, M. Inhibition of ADAM-TS4 and ADAM-TS5 Prevents Aggrecan Degradation in Osteoarthritic Cartilage J. Biol. Chem. 2002, 277, 22201-22208 10.1074/jbc.M200431200
4. Fajardo, M.; Di Cesare, P. E. Disease-Modifying Therapies for Osteoarthritis: Current Status Drugs Aging 2005, 22, 141-164 10.2165/00002512-200522020-00005
5. Porter, S.; Clark, I. M.; Kevorkian, L.; Edwards, D. R. The ADAMTS Metalloproteinases Biochem. J. 2005, 386, 15-27 10.1042/BJ20040424
6. Song, R.-H.; Tortorella, M. D.; Malfait, A. M.; Alston, J. T.; Yang, Z.; Arner, E. C.; Griggs, D. W. Aggrecan Degradation in Human Articular Cartilage Explants Is Medicated by Both ADAMTS-4 and ADAMTS-5 Arthritis Rheum. 2007, 56, 575-585 10.1002/art.22334
7. Gilbert, A. M.; Bikker, J. A.; O'Neil, S. V. Advances in the Development of Novel Aggrecanase Inhibitors Expert Opin. Ther. Pat. 2011, 21 (1) 1-12 10.1517/13543776.2011.539204
8. Renkiewicz, R.; Qiu, L.; Lesch, C.; Sun, X.; Devalaraja, R.; Cody, T.; Kaldjian, E.; Welgus, H.; Baragi, V. Broad-Spectrum Matrix Metalloproteinase Inhibitor Marimastat-Induced Musculoskeletal Side Effects in Rats Arthritis Rheum. 2003, 48, 1742-49 10.1002/art.11030
9. Hopper, D. W.; Vera, M. D.; How, D.; Sabatini, J.; Xiang, J. S.; Ipek, M.; Thomason, J.; Hu, Y.; Feyfant, E.; Wang, Q.; Georgiadis, K. E.; Reifenberg, E.; Sheldon, R. T.; Keohan, C. C.; Majumdar, M. K.; Morris, E. A.; Skotnicki, J.; Sum, P. Synthesis and Biological Evaluation of ((4-Keto)-phenoxy)methylbiophenyl-4-sulfonamides: A Class of Potent Aggrecanase-1 Inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 2487-2491 10.1016/j.bmcl.2009.03.056
10. Durham, T. B.; Klimkowski, V. J.; Rito, C. J.; Marimuthu, J.; Toth, J. L.; Liu, C.; Durbin, J. D.; Stout, S. L.; Swearingen, C.; Lin, C.; Chambers, M. G.; Thirunavukkarasu, K.; Wiley, M. R. Identification of Potent and Selective Hydantoin Inhibitors of Aggrecanase-1 and Aggrecanase-2 That Are Efficacious in Both Chemical and Surgical Models of Osteoarthritis J. Med. Chem. 2014, 57 (24) 10476-10485 10.1021/jm501522n
11. Clark, M. A.; Acharya, R. A.; Arico-Muendel, C. C.; Belyanskaya, S. L.; Benjamin, D. R.; Carlson, N. R.; Centrella, P. A.; Chiu, C. H.; Creaser, S. P.; Cuozzo, J. W.; Davie, C. P.; Ding, Y.; Franklin, G. J.; Franzen, K. D.; Gefter, M. L.; Hale, S. P.; Hansen, N. J. V.; Israel, D. I.; Jiang, J.; Kavarana, M. J.; Kelley, M. S.; Kollmann, C. S.; Li, F.; Lind, K.; Mataruse, S.; Medeiros, P. F.; Messer, J. A.; Myers, P.; O'Keefe, H.; Oliff, M. C.; Rise, C. E.; Satz, A. L.; Skinner, S. R.; Svendsen, J. L.; Tang, L.; Vloten, K. V.; Wagner, R. W.; Yao, G.; Zhao, B.; Morgan, B. A. Design, Synthesis and Selection of DNA-Encoded Small-Molecule Libraries Nat. Chem. Biol. 2009, 5, 647-654 10.1038/nchembio.211
12. Brenner, S.; Lerner, R. A. Encoded Combinatorial Chemistry Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 5381-5383 10.1073/pnas.89.12.5381
13. Kleiner, R. E.; Dumelin, C. E.; Liu, D. R. Small-Molecule Discovery from DNA-Encoded Chemical Libraries Chem. Soc. Rev. 2011, 40, 5707-5717 10.1039/c1cs15076f
14. Mannocci, L.; Leimbacher, M.; Wichert, M.; Scheuermann, J.; Neri, D. 20 Years of DNA-Encoded Chemical Libraries Chem. Commun. 2011, 47, 12747-12753 10.1039/c1cc15634a
15. Halpin, D. R.; Harbury, P. B. DNA Display II. Genetic Manipulation of Combinatorial Chemistry Libraries for Small-molecule Evolution PLoS Biol. 2004, 2, e174 10.1371/journal.pbio.0020174
16. Connors, W. H.; Hale, S. P.; Terrett, N. K. DNA-Encoded Chemical Libraries of Macrocycles Curr. Opin. Chem. Biol. 2015, 26, 42-47 10.1016/j.cbpa.2015.02.004
17. Deng, H.; O'Keefe, H.; Davie, C. P.; Lind, K. E.; Acharya, R. A.; Franklin, G. J.; Larkin, J.; Matico, R.; Neeb, M.; Thompson, M. M.; Lohr, T.; Gross, J. W.; Centrella, P. A.; O'Donovan, G. K.; Bedard, K. L.; Vloten, K.-v.; Mataruse, S.; Skinner, S. R.; Belyanskaya, S. L.; Carpenter, T. Y.; Shearer, T. W.; Clark, M. A.; Cuozzo, J. W.; Arico-Muendel, C. C.; Morgan, B. A. Discovery of Highly Potent and Selective Small Molecule ADAMTS-5 Inhibitors That Inhibit Human Cartilage Degradation via Encoded Library Technology (ELT) J. Med. Chem. 2012, 55, 7061-7079 10.1021/jm300449x
18. Disch, J. S.; Evindar, G.; Chiu, C. H.; Blum, C. A.; Dai, H.; Jin, L.; Schuman, E.; Lind, K. E.; Belyanskaya, S. L.; Deng, J.; Coppo, F.; Aquilani, L.; Graybill, T. L.; Cuozzo, J. W.; Lavu, S.; Mao, C.; Vlasuk, G. P.; Perni, R. B. Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3 J. Med. Chem. 2013, 56, 3666-3679 10.1021/jm400204k
19. Thalji, R. K.; McAtee, J. J.; Belyanskaya, S.; Brandt, M.; Brown, G. D.; Costell, M. H.; Ding, Y.; Dodson, J. W.; Eisennagel, S. H.; Fries, R. E.; Gross, J. W.; Harpel, M. R.; Holt, D. A.; Israel, D. I.; Jolivette, L. J.; Krosky, D.; Li, H.; Lu, Q.; Mandichak, T.; Roethke, T.; Schnackenberg, C. G.; Schwartz, B.; Shewchuk, L. M.; Xie, W.; Behm, D. J.; Douglas, S. A.; Shaw, A. L.; Marino, J. P., Jr. Discovery of 1-(1,3,5-Triazin-2-yl)piperidine-4-carboxamides as Inhibitors of Soluble Epoxide Hydrolase Bioorg. Med. Chem. Lett. 2013, 23, 3584-3588 10.1016/j.bmcl.2013.04.019
20. Encinas, L.; O'Keefe, H.; Neu, M.; Remuiñán, M. J.; Patel, A. M.; Guardia, A.; Davie, C. P.; Pérez-Macías, N.; Yang, H.; Convery, M. A.; Messer, J. A.; Pérez-Herrán, E.; Centrella, P. A.; álvarez-Gómez, D.; Clark, M. A.; Huss, S.; O'Donovan, G. K.; Ortega-Muro, F.; McDowell, W.; Castañeda, P.; Arico-Muendel, C. C.; Pajk, S.; Rullás, J.; Angulo-Barturen, I.; álvarez-Ruíz, E.; Mendoza-Losana, A.; Pages, L. B.; Castro-Pichel, J.; Evindar, G. Encoded Library Technology as a Source of Hits for the Discovery and Lead Optimization of a Potent and Selective Class of Bactericidal Direct Inhibitors of Mycobacterium tuberculosis InhA J. Med. Chem. 2014, 57, 1276-1288 10.1021/jm401326j
21. Kollmann, C. S.; Bai, X.; Tsai, C.-H.; Yang, H.; Lind, K. E.; Skinner, S. R.; Zhu, Z.; Israel, D. I.; Cuozzo, J. W.; Morgan, B. A.; Yuki, K.; Xie, C.; Springer, T. A.; Shimaoka, M.; Evindar, G. Application of Encoded Library Technology (ELT) to a Protein-protein Interaction Target: Discovery of a Potent Class of Integrin Lymphocyte Function-associated Antigen 1 (LFA-1) Antagonists Bioorg. Med. Chem. 2014, 22, 2353-2365 10.1016/j.bmc.2014.01.050