Phosphoinositide-3-kinases (PI3Ks): Combined comparative modeling and 3D-QSAR to rationalize the inhibition of p110α

Journal of Chemical Information and Modeling

Volumn 48, Issue 3, 2008, Pages 629-638

  Frédérick, Raphaël ^a,b   Denny, William A ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b UNIVERSITY OF NAMUR   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

COMPUTER SIMULATION; DRUG THERAPY; FREE ENERGY;

DRUG DEVELOPMENT; INTEGRATED INTERACTION MODEL;

ONCOLOGY;

1 PHOSPHATIDYLINOSITOL 3 KINASE P110 SUBUNIT, MOUSE; 1-PHOSPHATIDYLINOSITOL 3-KINASE P110 SUBUNIT, MOUSE; PHOSPHATIDYLINOSITOL 3 KINASE;

ARTICLE; CHEMICAL STRUCTURE; DRUG ANTAGONISM; METABOLISM; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; MODELS, MOLECULAR; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 42149156181     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci700348m     Document Type: Article

References (30)

1. Cantley, L. C. The phosphoinositide 3-kinase pathway. Science 2002, 296, 1655-1657.
2. Leevers, S. J.; Vanhaesebroeck, B.; Waterfield, M. D. Signalling through phosphoinositide 3-kinases: the lipids take centre stage. Curr. Opin. Cell. Biol. 1999, 11, 219-225.
3. Katso, R.; Okkenhaug, K.; Ahmadi, K.; White, S.; Timms, J.; Waterfield, M. D. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu. Rev. Cell. Dev. Biol. 2001, 17, 615-675.
4. Stephens, L.; Williams, R.; Hawkins, P. Phosphoinositide 3-kinases as drug targets in cancer. Curr. Opin. Pharmacol. 2005, 5, 357-365.
5. Gymnopoulos, M.; Elsliger, M. A.; Vogt, P. K. Rare cancer-specific mutations in PIK3CA show gain of function. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 5569-5574.
6. Samuels, Y.; Wang, Z.; Bardelli, A.; Silliman, N.; Ptak, J.; Szabo, S.; Yan, H.; Gazdar, A.; Powell, S. M.; Riggins, G. J.; Willson, J. K.; Markowitz, S.; Kinzler, K. W.; Vogelstein, B.; Velculescu, V. E. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004, 304, 554.
7. Vogt, P. K.; Kang, S.; Elsliger, M. A.; Gymnopoulos, M. Cancer-specific mutations in phosphatidylinositol 3-kinase. Trends Biochem. Sci. 2007, 32, 342-349.
8. Cantley, L. C.; Neel, B. G. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 4240-4245.
9. Foukas, L. C.; Claret, M.; Pearce, W.; Okkenhaug, K.; Meek, S.; Peskett, E.; Sancho, S.; Smith, A. J.; Withers, D. J.; Vanhaesebroeck, B. Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature 2006, 441, 366-370.
10. Hayakawa, M.; Kaizawa, H.; Kawaguchi, K.; Ishikawa, N.; Koizumi, T.; Ohishi, T.; Yamano, M.; Okada, M.; Ohta, M.; Tsukamoto, S.; Raynaud, F. I.; Waterfield, M. D.; Parker, P.; Workman, P. Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110alpha inhibitors. Bioorg. Med. Chem. 2007, 15, 403-412.
11. Hayakawa, M.; Kaizawa, H.; Moritomo, H.; Koizumi, T.; Ohishi, T.; Okada, M.; Ohta, M.; Tsukamoto, S.; Parker, P.; Workman, P.; Waterfield, M. Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110alpha inhibitors. Bioorg. Med. Chem. 2006, 14, 6847-6858.
12. Hayakawa, M.; Kaizawa, H.; Moritomo, H.; Koizumi, T.; Ohishi, T.; Yamano, M.; Okada, M.; Ohta, M.; Tsukamoto, S.; Raynaud, F. I.; Workman, P.; Waterfield, M. D.; Parker, P. Synthesis and biological evaluation of pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine derivatives as novel PI3 kinase p110alpha inhibitors. Bioorg. Med. Chem. Lett. 2007, 17, 2438-2442.
13. Hayakawa, M.; Kawaguchi, K. I.; Kaizawa, H.; Koizumi, T.; Ohishi, T.; Yamano, M.; Okada, M.; Ohta, M.; Tsukamoto, S. I.; Raynaud, F. I.; Parker, P.; Workman, P.; Waterfield, M. D. Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors. Bioorg. Med. Chem. 2007, 15, 5837-5844.
14. Zhao, J. J.; Cheng, H.; Jia, S.; Wang, L.; Gjoerup, O. V.; Mikami, A.; Roberts, T. M. The p110alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 16296-16300.
15. Ruckle, T.; Schwarz, M. K.; Rommel, C. PI3Kgamma inhibition: towards an 'aspirin of the 21st century'. Nat. Rev. Drug Discovery 2006, 5, 903-918.
16. Ali, K.; Bilancio, A.; Thomas, M.; Pearce, W.; Gilfillan, A. M.; Tkaczyk, C.; Kuehn, N.; Gray, A.; Giddings, J.; Peskett, E.; Fox, R.; Bruce, I.; Walker, C.; Sawyer, C.; Okkenhaug, K.; Finan, P.; Vanhaesebroeck, B. Essential role for the p110delta phosphoinositide 3-kinase in the allergic response. Nature 2004, 431, 1007-1011.
17. Jackson, S. P.; Schoenwaelder, S. M.; Goncalves, I.; Nesbitt, W. S.; Yap, C. L.; Wright, C. E.; Kenche, V.; Anderson, K. E.; Dopheide, S. M.; Yuan, Y.; Sturgeon, S. A.; Prabaharan, H.; Thompson, P. E.; Smith, G. D.; Shepherd, P. R.; Daniele, N.; Kulkarni, S.; Abbott, B.; Saylik, D.; Jones, C.; Lu, L.; Giuliano, S.; Hughan, S. C.; Angus, J. A.; Robertson, A. D.; Salem, H. H. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat. Med. 2005, 11, 507-514.
18. Walker, E. H.; Perisic, O.; Ried, C.; Stephens, L.; Williams, R. L. Structural insights into phosphoinositide 3-kinase catalysis and signal-ling. Nature 1999, 402, 313-320.
19. Walker, E. H.; Pacold, M. E.; Perisic, O.; Stephens, L.; Hawkins, P. T.; Wymann, M. P.; Williams, R. L. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol. Cell. 2000, 6, 909-919.
20. Knight, Z. A.; Gonzalez, B.; Feldman, M. E.; Zunder, E. R.; Goldenberg, D. D.; Williams, O.; Loewith, R.; Stokoe, D.; Balla, A.; Toth, B.; Balla, T.; Weiss, W. A.; Williams, R. L.; Shokat, K. M. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell 2006, 125, 733-747.
21. Lambert, C.; Leonard, N.; De Bolle, X.; Depiereux, E. ESyPred3D: Prediction of proteins 3D structures. Bioinformatics 2002, 18, 1250-1256.
22. Marti-Renom, M. A.; Smart, A. C.; Fiser, A.; Sanchez, R.; Melo, F.; Sali, A. Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct. 2000, 29, 291-325.
23. Delano, W. L. The PyMOL Molecular Graphics System on World Wide Web. http://pymol.sourceforge.net/ (accessed Dec 10, 2007).
24. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.
25. Ferrara, P.; Gohlke, H.; Price, D. J.; Klebe, G.; Brooks, C. L., III Assessing scoring functions for protein-ligand interactions. J. Med. Chem. 2004, 47, 3032-3047.
26. Warren, G. L.; Andrews, G. W.; Capelli, A. M.; Clarke, B.; LaLonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S.; Tedesco, G.; Wall, I. D.; Woolven, J. M.; Peishoff, C. E.; Head, M. S. A critical assessment of docking programs and scoring functions. J. Med. Chem. 2006, 49, 5912-5931.
27. Altschul, S. F.; Madden, T. L.; Schaffer, A. A.; Zhang, J.; Zhang, Z.; Miller, W.; Lipman, D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25, 3389-3402.
28. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235-242.
29. Laskowski, R. A. PDBsum: summaries and analyses of PDB structures. Nucleic Acids Res. 2001, 29, 221-222.
30. SYBYL Version 7.3; Tripos International: St. Louis, MO, 2004.