Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 23, 2011, Pages 7155-7165

  Moffett, Kristofer ^a   Konteatis, Zenon ^a   Nguyen, Duyan ^a   Shetty, Rupa ^a   Ludington, Jennifer ^a   Fujimoto, Ted ^a   Lee, Kyoung Jin ^a   Chai, Xiaomei ^a   Namboodiri, Haridasan ^a   Karpusas, Michael ^a   Dorsey, Bruce ^a   Guarnieri, Frank ^a   Bukhtiyarova, Marina ^a   Springman, Eric ^a   Michelotti, Enrique ^a  

^a Ansaris   (United States)

Author keywords

DFG out conformation; p38 Kinase; Virtual fragment based drug design

Indexed keywords

ARGININE; ASPARTIC ACID; DEXAMETHASONE; GLUTAMIC ACID; MITOGEN ACTIVATED PROTEIN KINASE P38; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; THIOMORPHOLINE DERIVATIVE;

ALPHA HELIX; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG CONFORMATION; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; HUMAN; HUMAN CELL; HYDROGEN BOND; IC 50; MOLECULAR INTERACTION; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; RAT; SUBSTITUTION REACTION; VIRTUAL FRAGMENT BASED DRUG DESIGN; X RAY CRYSTALLOGRAPHY;

ADENOSINE TRIPHOSPHATE; ANIMALS; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; DEXAMETHASONE; DRUG DISCOVERY; ENZYME ACTIVATION; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; MICE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OLIGOPEPTIDES; P38 MITOGEN-ACTIVATED PROTEIN KINASES; RATS; THIOPHENES;

EID: 80255138640     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.09.078     Document Type: Article

References (25)

1. E.H.S. Choy, and G.S. Panayi New Eng. J. Med. 344 2001 907
2. C.A. Dinarello Curr. Opin. Immunol. 3 1991 941
3. B. Jarvis, and D. Faulds Drugs 57 1999 945
4. H.E. Seymour, A. Worsley, J.M. Smith, and S.H.L. Thomas Br. J. Clin. Pharmacol. 51 2001 201
5. P.J. Rutgeerts Aliment. Pharmacol. Ther. 13 1999 9
6. J. Westra, and P.C. Limburg Mini-Rev. Med. Chem. 6 2006 867
7. K.K. Hale, D. Trollinger, M. Rihanek, and C.L. Mantley J. Immunol. 162 1999 4246
8. A. Korb, M. Tohidast-Akrad, E. Cetin, R. Axmann, J. Smolen, and G. Schett Arthritis Rheum. 54 2006 2745
9. G. Schett, M. Tohidast-Akrad, J.S. Smolen, B.J. Schmid, C.W. Steiner, P. Bitzan, P. Zenz, K. Redlich, Q. Xu, and G. Steiner Arthritis Rheum. 43 2000 2501
10. D.M. Goldstein, and T. Gabriel Curr. Top. Med. Chem. 5 2005 1017
11. L.H. Pettus, and R.P. Wurtz Curr. Top. Med. Chem. 8 2008 1452
12. M.C. Genovese Arthritis Rheum. 60 2009 317
13. D.M. Goldstein, A. Kuglstatter, Y. Lou, and M.J. Soth J. Med. Chem. 53 2010 2345
14. S.E. Tong, S.E. Daniels, T. Montano, S. Chang, and P. Desjardins Am. Soc. Clin. Pharmcol. Ther. 75 2004 1
15. M.A. Fabian, W.H. Biggs III, D.K. Treiber, C.E. Atteridge, M.D. Azimioara, M.G. Benedetti, T.A. Carter, P. Ciceri, P.T. Edeen, M. Floyd, J.M. Ford, M. Galvin, J.L. Gerlach, R.M. Grotzfeld, S. Herrgard, D.E. Insko, M.A. Insko, A.G. Lai, J.M. Lelias, S.A. Mehta, Z.V. Milanov, A.M. Velasco, L.M. Wodicka, H.K. Patel, P.P. Zarrinkar, and D.J. Lockhart Nat. Biotechnol. 23 2005 329
16. A. Cuenda, J. Rouse, Y.N. Doza, R. Meier, P. Cohen, T.F. Gallagher, P.R. Young, and J.C. Lee FEBS Lett. 364 1995 229
17. C. Pargellis, L. Tong, L. Churchill, P.F. Cirillo, T. Gilmore, A.G. Graham, P.M. Grob, E.R. Hickey, N. Moss, S. Pav, and J. Regan Nat. Struct. Biol. 9 2002 268
18. J. Regan, S. Breitfelder, P. Cirillo, T. Gilmore, A.G. Graham, E. Hickley, B. Klaus, J. Madwed, M. Moriak, N. Moss, C. Pargelis, S. Pav, A. Proto, A. Swinamer, L. Tong, and C. Torcellini J. Med. Chem. 45 2002 2994
19. H. Liu, C. Kuhn, F. Feru, S.L. Jacques, G.D. Deshmukh, P. Ye, G.R. Rennie, T. Johnson, S. Kazmirski, S. Low, R. Coli, Y.-H. Ding, A.C. Cheng, H. Tecle, J.M. English, R. Stanton, and J.C. Wub Bioorg. Med. Chem. Lett. 20 2010 4885
20. Y.M. Ahn, M. Clare, C.L. Ensinger, M.M. Hood, J.W. Lord, W.-P. Lu, D.F. Miller, W.C. Patt, B.D. Smith, L. Vogeti, M.D. Kaufman, P.A. Petillo, S.C. Wise, J. Abendroth, L. Chun, R. Clark, M. Feese, H. Kim, L. Stewart, and D.L. Flynn Bioorg. Med. Chem. Lett. 20 2010 5793
21. M. Clark, F. Guarnieri, I. Shkurko, and J. Wiseman J. Chem. Inf. Model. 46 2006 231
22. M. Clark, S. Meshkat, G.T. Talbot, P. Carnevali, and J.S. Wiseman J. Chem. Inf. Model. 49 2009 1901
23. J. Dumas, H. Hatoum-Mokdad, R. Sibley, B. Riedl, W.J. Scott, M.K. Monahan, T.B. Lowinger, C. Brennan, R. Natero, T. Turner, J.S. Johnson, R. Schoenleber, A. Bhargava, S.M. Wilhelm, T.J. Housley, G.E. Ranges, and A. Shrikhande Bioorg. Med. Chem. Lett. 10 2000 2051
24. A.M. Redman, J.S. Johnson, R. Dally, S. Swartz, H. Wild, H. Paulsen, Y. Caringal, D. Gunn, J. Renick, M. Osterhout, J. Kingery-Wood, R.A. Smith, W. Lee, J. Dumas, S.M. Wilhelm, T.J. Housley, A. Bhargava, G.E. Ranges, A. Shrikhande, D. Young, M. Bombara, and W.J. Scott Bioorg. Med. Chem. Lett. 11 2001 9
25. Ranges, G.; Scott, W.; Bombara, M.; Rauner, D.; Redman, A.; Smith, R.; Paulsen, H.; Chen, J.; Gunn, D.; Renick, J. PCT Int. Appl. WO 98/52558, 1998.