Identification of peroxisome proliferator-activated receptor ligands from a biased chemical library

Chemistry and Biology

Volumn 4, Issue 12, 1997, Pages 909-918

  Brown, Peter J ^a   Smith Oliver, Tracey A ^a   Charifson, Paul S ^a,b   Tomkinson, Nicholas C O ^a   Fivush, Adam M ^a   Sternbach, Daniel D ^a   Wade, Laura E ^a   Orband Miller, Lisa ^a   Parks, Derek J ^a   Blanchard, Steven G ^a   Kliewer, Steven A ^a   Lehmann, Jürgen M ^a   Willson, Timothy M ^a  

^a GLAXOSMITHKLINE   (United States)

^b VERTEX PHARMACEUTICALS   (United States)

Author keywords

Combinatorial chemistry; Fibrate; Nuclear receptor; Orphan receptor; Solid phase synthesis

Indexed keywords

EID: 13144283625     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1074-5521(97)90299-4     Document Type: Article

References (35)

1. Mangelsdorf, D.J. & Evans, R.M. (1995). The RXR heterodimers and orphan receptors. Cell 83, 841-850.
2. Lemberger, T., Desvergne, B. & Wahli, W. (1996). Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu. Rev. Cell Dev. Biol. 12, 335-363.
3. Kliewer, S.A. et al., & Evans, R.M. (1994). Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl Acad. Sci. USA 91, 7355-7359.
4. Willson, T.M. & Wahli, W. (1997). Peroxisome proliferator-activated receptor agonists. Curr. Opin. Chem. Biol. 1, 235-241.
5. Schoonjans, K., Martin, G., Staels, B. & Auwerx, J. (1997). Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr. Opin. Lipidol. 8, 159-166.
6. Wahli, W., Braissant, O. & Desvergne, B. (1995). Peroxisome proliferator activated receptors: transcriptional regulators of adipogenesis, lipid metabolism and more... Chem. Biol. 2, 261-266.
7. Staels, B. & Auwerx, J. (1997). Role of PPAR in the pharmacological regulation of lipoprotein metabolism by fibrates and thiazolidinediones. Curr. Pharm. Des. 3, 1-14.
8. Kliewer, S.A. et al., & Lehmann, J.M. (1997). Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ. Proc. Natl Acad. Sci. USA 94, 4318-4323.
9. Forman, B.M., Chen, J. & Evans, R.M. (1997). Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ. Proc. Natl Acad. Sci. USA 94, 4312-4317.
10. Krey, G. et al., & Wahli, W. (1997). Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol. Endocrinol. 11, 779-791.
11. Schmidt, A., Endo, N., Rutledge, S.J., Vogel, R., Shinar, D. & Rodan, G.A. (1992). Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol. Endocrinol. 6, 1634-1641.
12. Amri, E.-Z., Bonino, F., Ailhaud, G., Abumrad, N.A. & Grimaldi, P.A. (1995). Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors. J. Biol. Chem. 270, 2367-2371.
13. Pavia, M.R. (1997). Combinatorial chemistry: a perspective. Annu. Rep. Comb. Chem. Mol. Diversity 1, 3-5.
14. Gallop, M.A, Barrett, R.W., Dower, W.J., Fodor, S.P.A. & Gordon, E.M. (1994). Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. J. Med. Chem. 37, 1233-1251.
15. Gordon, E.M, Barrett, R.W., Dower, W.J., Fodor, S.P.A. & Gallop, M.A. (1994). Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. J. Med. Chem. 37, 1385-1401.
16. Gaw, A., Packard, C.J. & Shepherd, J. (1994). Fibrates. Handb. Exp. Pharmacol. 109, 325-348.
17. Brown, P.J., Hurley, K.P., Stuart, LW. & Willson, T.M. (1997). Generation of secondary alkyl amines on solid support by borane reduction: application to the parallel synthesis of PPAR ligands. Synthesis 778-782.
18. Johnson, M.E., Moore, L.M. & Ylvisaker, D. (1990). Minimax and maximin distance designs. J. Stat. Plan. Infer. 26, 131-148.
19. Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., Wilkison, W.O., Willson, T.M. & Kliewer, S.A. (1995). An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J. Biol. Chem. 270, 12953-12956.
20. McDonnell, D.P., Vegeto, E. & Gleeson, MAG. (1993). Nuclear hormone receptors as targets for new drug discovery. Bio/Technology 11, 1256-1261.
21. Heck, R.F. (1982). Palladium-catalyzed vinylation of organic halides. Org. React. 27, 345-390.
22. Fukuyama, T., Jow, C.K. & Cheung, M. (1995). 2- and 4-Nitrobenzenesulfonamides: exceptionally versatile means for preparation of secondary amines and protection of amines. Tetrahedron Lett. 36, 6373-6374.
23. Thorp, J.M. (1963). An experimental approach to the problem of disordered lipid metabolism. J. Atherosclerosis Res. 3, 351-360.
24. Zammit, V.A. (1984). Mechanisms of regulation of the partition of fatty acids between oxidation and esterification in the liver. Prog. Lipid Res. 23, 39-67.
25. Issemann, I., Prince, R.A., Tugwood, J.D. & Green, S. (1993). The peroxisome proliferator-activated receptor:retinoid X receptor heterodimer is activated by fatty acids and fibrate hypolipemic drugs. J. Mol. Endocrinol. 11, 37-47.
26. Goettlicher, M., Demoz, A., Svensson, D., Tollet, P., Berge, R.K. & Gustafsson, J.A. (1993). Structural and metabolic requirements for activators of the peroxisome proliferator-activated receptor. Biochem. Pharmacol. 46, 2177-2184.
27. Mangelsdorf, D.J., et al., & Evans, R.M. (1995). The nuclear receptor superfamily: the second decade. Cell 83, 835-839.
28. Enmark, E. & Gustafsson, J.A. (1996). Orphan nuclear receptors - the first eight years. Mol. Endocrinol. 10, 1293-1307.
29. Weininger, D. (1988). SMILES, a chemical language and information-system. 1. Introduction to methodology and encoding rules. J. Chem. Info. Compt. Sci. 28, 31-36.
30. Pearlman, R.S. (1987). Rapid generation of high quality approximate 3D molecular structures. Chem. Des. Aut. News. 2, 1-6.
31. Lambert, M.H. (1997). Docking conformationally flexible molecules into protein binding sites. In Practical Applications of Computer-Aided Drug Design. (Charifson, P.S., ed.), pp 243-303; Marcel Dekker, New York.
32. SAS Institute Inc. (1995). SAS/QC Software: Usage and Reference, Version 6. (1st edn), pp. 704-728, SAS Institute Inc., Cary, NC.
33. Willson, T.M., et al., & Lehmann, J.M. (1996). The structure activity relationship between peroxisome proliferator-activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones. J. Med. Chem. 39, 665-668.
34. Lorenz, J.J., et al., & Gray, J.G. (1995). A cyclic adenosine 3′,5′-monophosphate signal is required for the induction of IL-1β by TNF-α in human monocytes. J. Immunol. 155, 836-844.
35. Berger, J., Hauber, R., Geiger, R. & Cullen, B.R. (1988). Secreted alkaline phosphatase: a powerful new quantitative indicator of gene expression in eukaryotic cells. Gene 66, 1-10.