A back-to-front fragment-based drug design search strategy targeting the DFG-out pocket of protein tyrosine kinases

ACS Medicinal Chemistry Letters

Volumn 3, Issue 4, 2012, Pages 342-346

  Iwata, Hidehisa ^a   Oki, Hideyuki ^a   Okada, Kengo ^a   Takagi, Terufumi ^a   Tawada, Michiko ^a   Miyazaki, Yasushi ^a   Imamura, Shinichi ^a   Hori, Akira ^a   Lawson, J David ^b   Hixon, Mark S ^b   Kimura, Hiroyuki ^a   Miki, Hiroshi ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b Takeda San Diego Inc   (United States)

Author keywords

back to front; DFG out; FBDD; phosphorylation; VEGFR2; Yonetani Theorell Plot

Indexed keywords

ADENOSINE TRIPHOSPHATE; PROTEIN TYROSINE KINASE; VASCULOTROPIN RECEPTOR 2;

ARTICLE; BINDING AFFINITY; CHEMICAL STRUCTURE; CRYSTALLIZATION; DRUG DESIGN; DRUG TARGETING; ENZYME PHOSPHORYLATION; FRAGMENT BASED DRUG DESIGN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROTEIN BINDING; SCREENING TEST;

EID: 84859743432     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml3000403     Document Type: Article

References (23)

1. Manning, G.; Whyte, D. B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome Science 2002, 298, 1912-1934 (Pubitemid 35425239)
2. Hunter, T. The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine: its role in cell growth and disease Philos. Trans. R. Soc., B 1998, 353, 583-605 (Pubitemid 28314105)
3. Schwartz, P. A.; Murray, B. W. Protein kinase biochemistry and drug discovery Bioorg. Chem. 2011, 39, 192-210
4. Blume-Jensen, P.; Hunter, T. Oncogenic kinase signalling Nature 2001, 411, 355-365 (Pubitemid 32467045)
5. Hubbard, S. R.; Mohammadi, M.; Schlessinger, J. Autoregulatory mechanisms in protein-tyrosine kinases J. Biol. Chem. 1998, 273, 11987-11990 (Pubitemid 28240552)
6. Adams, J. A. Activation Loop Phosphorylation and Catalysis in Protein Kinases: Is There Functional Evidence for the Autoinhibitor Model? Biochemistry 2002, 42, 601-607 (Pubitemid 36133283)
7. Pargellis, C.; Tong, L.; Churchill, L.; Cirillo, P. F.; Gilmore, T.; Graham, A. G.; Grob, P. M.; Hickey, E. R.; Moss, N.; Pav, S.; Regan, J. Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site Nat. Struct. Biol. 2002, 9, 268-272 (Pubitemid 34289898)
8. Iwata, H.; Imamura, S.; Hori, A.; Hixon, M. S.; Kimura, H.; Miki, H. Biochemical Characterization of TAK-593, a Novel VEGFR/PDGFR Inhibitor with a Two-Step Slow Binding Mechanism Biochemistry 2011, 50, 738-751
9. Liao, J. J.-L. Molecular Recognition of Protein Kinase Binding Pockets for Design of Potent and Selective Kinase Inhibitors J. Med. Chem. 2007, 50, 409-424 (Pubitemid 46239775)
10. Liu, Y.; Gray, N. S. Rational design of inhibitors that bind to inactive kinase conformations Nat. Chem. Biol. 2006, 2, 358-364 (Pubitemid 43936934)
11. Rees, D. C.; Congreve, M.; Murray, C. W.; Carr, R. Fragment-based lead discovery Nat. Rev. Drug Dicovery 2004, 3, 660-672 (Pubitemid 39173507)
12. Congreve, M.; Carr, R.; Murray, C.; Jhoti, H. A 'Rule of Three' for fragment-based lead discovery? Drug Discovery Today 2003, 8, 876-877 (Pubitemid 37194496)
13. Congreve, M.; Chessari, G.; Tisi, D.; Woodhead, A. J. Recent developments in fragment-based drug discovery J. Med. Chem. 2008, 51, 3661-3680 (Pubitemid 351956496)
14. Freire, E. Do enthalpy and entropy distinguish first in class from best in class? Drug Discovery Today 2008, 13, 869-874
15. de Kloe, G. E.; Bailey, D.; Leurs, R.; de Esch, I. J. Transforming fragments into candidates: Small becomes big in medicinal chemistry Drug Discovery Today 2009, 14, 630-646
16. Baldwin, I.; Bamborough, P.; Haslam, C. G.; Hunjan, S. S.; Longstaff, T.; Mooney, C. J.; Patel, S.; Quinn, J.; Somers, D. O. Kinase array design, back to front: Biaryl amides Bioorg. Med. Chem. Lett. 2008, 18, 5285-5289
17. Müller, G.; Sennhenn, P. C.; Woodcock, T.; Neumann, L. The 'retro-design' concept for novel kinase inhibitors IDrugs 2010, 13, 457-466
18. Simard, J. R.; Kluter, S.; Grutter, C.; Getlik, M.; Rabiller, M.; Rode, H. B.; Rauh, D. A new screening assay for allosteric inhibitors of cSrc Nat. Chem. Biol. 2009, 5, 394-396
19. Simard, J. R.; Getlik, M.; Grutter, C.; Pawar, V.; Wulfert, S.; Rabiller, M.; Rauh, D. Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors J. Am. Chem. Soc. 2009, 131, 13286-13296
20. Iwata, H.; Imamura, S.; Hori, A.; Hixon, M. S.; Kimura, H.; Miki, H. Biochemical characterization of a novel type-II VEGFR2 kinase inhibitor: Comparison of binding to non-phosphorylated and phosphorylated VEGFR2 Bioorg. Med. Chem. 2011, 19, 5342-5351
21. Yonetani, T.; Theorell, H. Studies on liver alcohol dehydrogenase complexes: III. Multiple inhibition kinetics in the presence of two competitive inhibitors Arch. Biochem. Biophys. 1964, 106, 243-251
22. Yonetani, T. The Yonetani-Theorell graphical method for examining overlapping subsites of enzyme active centers Methods Enzymol. 1982, 87, 500-509
23. Oguro, Y.; Miyamoto, N.; Okada, K.; Takagi, T.; Iwata, H.; Awazu, Y.; Miki, H.; Hori, A.; Kamiyama, K.; Imamura, S. Design, synthesis, and evaluation of 5-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine derivatives: novel VEGFR2 kinase inhibitors binding to inactive kinase conformation Bioorg. Med. Chem. 2010, 18, 7260-7273