Dissecting fragment-based lead discovery at the von hippel-lindau protein:Hypoxia inducible factor 1α protein-protein interface

Chemistry and Biology

Volumn 19, Issue 10, 2012, Pages 1300-1312

  Van Molle, Inge ^a   Thomann, Andreas ^a   Buckley, Dennis L ^b   So, Ernest C ^a   Lang, Steffen ^a   Crews, Craig M ^b,c   Ciulli, Alessio ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b YALE UNIVERSITY   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 1ALPHA INHIBITOR; LEAD; LIGAND; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; VON HIPPEL LINDAU PROTEIN; VON HIPPEL LINDAU PROTEIN INHIBITOR;

ARTICLE; BINDING AFFINITY; BINDING SITE; BIOPHYSICS; COMPLEX FORMATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG TARGETING; FRAGMENT BASED LEAD DISCOVERY; FRAGMENTATION REACTION; HIGH THROUGHPUT SCREENING; LIPOPHILICITY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING;

BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MODELS, CHEMICAL; PROTEIN BINDING; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT PROTEINS; SMALL MOLECULE LIBRARIES; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 84868026890     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.chembiol.2012.08.015     Document Type: Article

References (52)

1. K. Babaoglu, and B.K. Shoichet Deconstructing fragment-based inhibitor discovery Nat. Chem. Biol. 2 2006 720 723 (Pubitemid 44764214)
2. L inhibitors J. Med. Chem. 53 2010 2577 2588
3. N. Basse, J.L. Kaar, G. Settanni, A.C. Joerger, T.J. Rutherford, and A.R. Fersht Toward the rational design of p53-stabilizing drugs: probing the surface of the oncogenic Y220C mutant Chem. Biol. 17 2010 46 56
4. A.C. Braisted, J.D. Oslob, W.L. Delano, J. Hyde, R.S. McDowell, N. Waal, C. Yu, M.R. Arkin, and B.C. Raimundo Discovery of a potent small molecule IL-2 inhibitor through fragment assembly J. Am. Chem. Soc. 125 2003 3714 3715 (Pubitemid 36512355)
5. D.L. Buckley, I. Van Molle, P.C. Gareiss, H.S. Tae, J. Michel, D.J. Noblin, W.L. Jorgensen, A. Ciulli, and C.M. Crews Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1α interaction J. Am. Chem. Soc. 134 2012 4465 4468
6. A. Ciulli, and C. Abell Fragment-based approaches to enzyme inhibition Curr. Opin. Biotechnol. 18 2007 489 496
7. A. Ciulli, G. Williams, A.G. Smith, T.L. Blundell, and C. Abell Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods J. Med. Chem. 49 2006 4992 5000 (Pubitemid 44201057)
8. M. Congreve, R. Carr, C. Murray, and H. Jhoti A 'rule of three' for fragment-based lead discovery? Drug Discov. Today 8 2003 876 877 (Pubitemid 37194496)
9. M. Congreve, G. Chessari, D. Tisi, and A.J. Woodhead Recent developments in fragment-based drug discovery J. Med. Chem. 51 2008 3661 3680 (Pubitemid 351956496)
10. A.G. Coyne, D.E. Scott, and C. Abell Drugging challenging targets using fragment-based approaches Curr. Opin. Chem. Biol. 14 2010 299 307
11. C.M. Crews Targeting the undruggable proteome: the small molecules of my dreams Chem. Biol. 17 2010 551 555
12. C. Dalvit, G. Fogliatto, A. Stewart, M. Veronesi, and B. Stockman WaterLOGSY as a method for primary NMR screening: practical aspects and range of applicability J. Biomol. NMR 21 2001 349 359 (Pubitemid 34071389)
13. F.N.B. Edfeldt, R.H.A. Folmer, and A.L. Breeze Fragment screening to predict druggability (ligandability) and lead discovery success Drug Discov. Today 16 2011 284 287
14. D.A. Erlanson, A.C. Braisted, D.R. Raphael, M. Randal, R.M. Stroud, E.M. Gordon, and J.A. Wells Site-directed ligand discovery Proc. Natl. Acad. Sci. USA 97 2000 9367 9372 (Pubitemid 30650781)
15. D.A. Erlanson, R.S. McDowell, and T. O'Brien Fragment-based drug discovery J. Med. Chem. 47 2004 3463 3482 (Pubitemid 38822007)
16. E.B. Fauman, B.K. Rai, and E.S. Huang Structure-based druggability assessment - identifying suitable targets for small molecule therapeutics Curr. Opin. Chem. Biol. 15 2011 463 468
17. P. Filippakopoulos, J. Qi, S. Picaud, Y. Shen, W.B. Smith, O. Fedorov, E.M. Morse, T. Keates, T.T. Hickman, and I. Felletar Selective inhibition of BET bromodomains Nature 468 2010 1067 1073
18. P.J. Hajduk, and J. Greer A decade of fragment-based drug design: strategic advances and lessons learned Nat. Rev. Drug Discov. 6 2007 211 219 (Pubitemid 46344625)
19. P.J. Hajduk, J.R. Huth, and S.W. Fesik Druggability indices for protein targets derived from NMR-based screening data J. Med. Chem. 48 2005 2518 2525 (Pubitemid 40516441)
20. P.J. Hajduk, W.R.J.D. Galloway, and D.R. Spring Drug discovery: A question of library design Nature 470 2011 42 43
21. A.P. Higueruelo, A. Schreyer, G.R.J. Bickerton, W.R. Pitt, C.R. Groom, and T.L. Blundell Atomic interactions and profile of small molecules disrupting protein-protein interfaces: the TIMBAL database Chem. Biol. Drug Des. 74 2009 457 467
22. W.-C. Hon, M.I. Wilson, K. Harlos, T.D.W. Claridge, C.J. Schofield, C.W. Pugh, P.H. Maxwell, P.J. Ratcliffe, D.I. Stuart, and E.Y. Jones Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL Nature 417 2002 975 978 (Pubitemid 34716877)
23. A.L. Hopkins, C.R. Groom, and A. Alex Ligand efficiency: a useful metric for lead selection Drug Discov. Today 9 2004 430 431 (Pubitemid 38510559)
24. P. Jaakkola, D.R. Mole, Y.M. Tian, M.I. Wilson, J. Gielbert, S.J. Gaskell, A.v. Kriegsheim, H.F. Hebestreit, M. Mukherji, and C.J. Schofield Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation Science 292 2001 468 472 (Pubitemid 32335942)
25. W.G. Kaelin Jr. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer Nat. Rev. Cancer 8 2008 865 873
26. D. Kozakov, D.R. Hall, G.-Y. Chuang, R. Cencic, R. Brenke, L.E. Grove, D. Beglov, J. Pelletier, A. Whitty, and S. Vajda Structural conservation of druggable hot spots in protein-protein interfaces Proc. Natl. Acad. Sci. USA 108 2011 13528 13533
27. H. Köster, T. Craan, S. Brass, C. Herhaus, M. Zentgraf, L. Neumann, A. Heine, and G. Klebe A small nonrule of 3 compatible fragment library provides high hit rate of endothiapepsin crystal structures with various fragment chemotypes J. Med. Chem. 54 2011 7784 7796
28. J.K. Kranz, and C. Schalk-Hihi Protein thermal shifts to identify low molecular weight fragments Methods Enzymol. 493 2011 277 298
29. A. Larsson, A. Jansson, A. Åberg, and P. Nordlund Efficiency of hit generation and structural characterization in fragment-based ligand discovery Curr. Opin. Chem. Biol. 15 2011 482 488
30. P.D. Leeson, and B. Springthorpe The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discov. 6 2007 881 890 (Pubitemid 350042396)
31. C. Loenarz, J. Mecinović, R. Chowdhury, L.A. McNeill, E. Flashman, and C.J. Schofield Evidence for a stereoelectronic effect in human oxygen sensing Angew. Chem. Int. Edit. Engl. 48 2009 1784 1787
32. J.J. Lundquist, and E.J. Toone The cluster glycoside effect Chem. Rev. 102 2002 555 578 (Pubitemid 35377623)
33. M. Mayer, and B. Meyer Characterization of ligand binding by saturation transfer difference NMR spectroscopy Angew. Chem. Int. Edit. Engl. 38 1999 1784 1788 (Pubitemid 29290947)
34. T. Maurer, L.S. Garrenton, A. Oh, K. Pitts, D.J. Anderson, N.J. Skelton, B.P. Fauber, B. Pan, S. Malek, and D. Stokoe Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity Proc. Natl. Acad. Sci. USA 109 2012 5299 5304
35. J.-H. Min, H. Yang, M. Ivan, F. Gertler, W.G. Kaelin Jr.; and N.P. Pavletich Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling Science 296 2002 1886 1889 (Pubitemid 34596278)
36. X. Morelli, R. Bourgeas, and P. Roche Chemical and structural lessons from recent successes in protein-protein interaction inhibition (2P2I) Curr. Opin. Chem. Biol. 15 2011 475 481
37. P.N. Mortenson, and C.W. Murray Assessing the lipophilicity of fragments and early hits J. Comput. Aided Mol. Des. 25 2011 663 667
38. C.W. Murray, and M.L. Verdonk The consequences of translational and rotational entropy lost by small molecules on binding to proteins J. Comput. Aided Mol. Des. 16 2002 741 753 (Pubitemid 36336183)
39. C.W. Murray, and D.C. Rees The rise of fragment-based drug discovery Nat. Chem. 1 2009 187 192
40. C.W. Murray, M.L. Verdonk, and D.C. Rees Experiences in fragment-based drug discovery Trends Pharmacol. Sci. 33 2012 224 232
41. M. Nazaré, H. Matter, D.W. Will, M. Wagner, M. Urmann, J. Czech, H. Schreuder, A. Bauer, K. Ritter, and V. Wehner Fragment deconstruction of small, potent factor Xa inhibitors: exploring the superadditivity energetics of fragment linking in protein-ligand complexes Angew. Chem. Int. Edit. Engl. 51 2012 905 911
42. M.I. Page, and W.P. Jencks Entropic contributions to rate accelerations in enzymic and intramolecular reactions and the chelate effect Proc. Natl. Acad. Sci. USA 68 1971 1678 1683
43. A.M. Petros, J. Dinges, D.J. Augeri, S.A. Baumeister, D.A. Betebenner, M.G. Bures, S.W. Elmore, P.J. Hajduk, M.K. Joseph, and S.K. Landis Discovery of a potent inhibitor of the antiapoptotic protein Bcl-xL from NMR and parallel synthesis J. Med. Chem. 49 2006 656 663 (Pubitemid 43157495)
44. G. Saxty, S.J. Woodhead, V. Berdini, T.G. Davies, M.L. Verdonk, P.G. Wyatt, R.G. Boyle, D. Barford, R. Downham, M.D. Garrett, and R.A. Carr Identification of inhibitors of protein kinase B using fragment-based lead discovery J. Med. Chem. 50 2007 2293 2296 (Pubitemid 46799240)
45. T.J. Stout, C.R. Sage, and R.M. Stroud The additivity of substrate fragments in enzyme-ligand binding Structure 6 1998 839 848 (Pubitemid 28348647)
46. Q. Sun, J.P. Burke, J. Phan, M.C. Burns, E.T. Olejniczak, A.G. Waterson, T. Lee, O.W. Rossanese, and S.W. Fesik Discovery of small molecules that bind to K-Ras and inhibit Sos-mediated activation Angew. Chem. Int. Edit. Engl. 51 2012 6140 6143
47. S. Surade, and T.L. Blundell Structural biology and drug discovery of difficult targets: the limits of ligandability Chem. Biol. 19 2012 42 50
48. P. Śledź, C.J. Stubbs, S. Lang, Y.-Q. Yang, G.J. McKenzie, A.R. Venkitaraman, M. Hyvönen, and C. Abell From crystal packing to molecular recognition: prediction and discovery of a binding site on the surface of polo-like kinase 1 Angew. Chem. Int. Edit. Engl. 50 2011 4003 4006
49. D.G. Teotico, K. Babaoglu, G.J. Rocklin, R.S. Ferreira, A.M. Giannetti, and B.K. Shoichet Docking for fragment inhibitors of AmpC beta-lactamase Proc. Natl. Acad. Sci. USA 106 2009 7455 7460
50. D.H.H. Tsao, A.G. Sutherland, L.D. Jennings, Y. Li, T.S. Rush 3rd, J.C. Alvarez, W. Ding, E.G. Dushin, R.G. Dushin, and S.A. Haney Discovery of novel inhibitors of the ZipA/FtsZ complex by NMR fragment screening coupled with structure-based design Bioorg. Med. Chem. 14 2006 7953 7961 (Pubitemid 44584704)
51. J.A. Wells, and C.L. McClendon Reaching for high-hanging fruit in drug discovery at protein-protein interfaces Nature 450 2007 1001 1009 (Pubitemid 350273630)
52. H. Yin, and A.D. Hamilton Strategies for targeting protein-protein interactions with synthetic agents Angew. Chem. Int. Edit. Engl. 44 2005 4130 4163 (Pubitemid 40982718)