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Chemical Compound Review

Fibrates     2-(4-chlorophenoxy)-2-methyl- propanoic acid

Synonyms: Regadrin, clofibric acid, NSC-1149, NSC1149, NSC 1149, ...
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Disease relevance of clofibric acid


High impact information on clofibric acid

  • Amphipathic carboxylates such as clofibric acid have been used in man as hypolipidaemic agents and in rodents they stimulate the proliferation of peroxisomes [5].
  • Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor [6].
  • Conversely, when a rat liver cytosol containing multiple members of the HSP70 family was passed through an ATP-agarose column, and eluted with clofibric acid, only P72 (HSC70) was eluted [7].
  • These results suggest that clofibric acid, a peroxisome proliferator, preferentially interacts with P72 at or near the ATP binding site [7].
  • We now show that this protein is homologous with the heat shock protein HSP70 family by analysis of amino acid sequences of isolated peptides from trypsin-treated clofibric acid binding protein and by cross-reactivity with a monoclonal antibody raised against the conserved region of the 70-kDa heat shock proteins [7].

Chemical compound and disease context of clofibric acid


Biological context of clofibric acid

  • However, clofibric acid did not significantly alter single nephron glomerular filtration rates (95 +/- 2.1 nl/min in treated versus 97.0 +/- 6.2 nl/min in untreated, p greater than 0.05) or glomerular capillary pressures (56.6 +/- 1.5 mm Hg in treated versus 57.8 +/- 0.8 mm Hg in untreated, p greater than 0.05) in 5/6 nephrectomy rats [1].
  • Liver gene expression profiles of rats treated with clofibric acid: comparison of whole liver and laser capture microdissected liver [13].
  • Gene transfer experiments indicate that induction by the peroxisome proliferators, clofibric acid and WY-14,643, of luciferase expression driven by the promoter and 5'-flanking sequences of the rabbit cytochrome P450 4A6 gene (CYP4A6) is dependent on cotransfection of expression plasmids for the peroxisome proliferator-activated receptor, PPAR [14].
  • Saliva and plasma levels and plasma protein binding of clofibrinic acid in uremic patients [15].
  • Elevated levels of 8-OHdG were not detected in DNA isolated from nuclear fractions of livers from rats fed clofibric acid for 22 weeks, indicating the dependence of PP-induced oxidative DNA damage on extranuclear components of samples for DNA isolation [16].

Anatomical context of clofibric acid


Associations of clofibric acid with other chemical compounds


Gene context of clofibric acid


Analytical, diagnostic and therapeutic context of clofibric acid

  • Using affinity chromatography, we had previously isolated a protein that binds to clofibric acid [7].
  • Inulin clearance was greater in clofibric acid-treated than in untreated 5/6 nephrectomy rats (0.28 +/- 0.02 versus 0.22 +/- 0.02 ml/min 100 g body wt, p less than 0.05) [1].
  • The free fraction of clofibrinic acid in plasma is higher (p less than 0.02) in long-term hemodialysis patients (0.0915 +/- 0.0141) than in nondialysis patients (0.0715 +/- 0.0143) [15].
  • RESEARCH DESIGN AND METHODS: Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study [2].
  • However, quantitation of a PCR amplified region from the D-loop of mtDNA demonstrated a 2- to 3-fold increase in the relative amount of mtDNA in DNA isolated from unfractionated liver homogenates following 3, 11, and 22 weeks exposure to Wy or CA (22 weeks only) [30].


  1. Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure. Kasiske, B.L., O'Donnell, M.P., Garvis, W.J., Keane, W.F. Circ. Res. (1988) [Pubmed]
  2. Diabetes Intervention Study. Multi-intervention trial in newly diagnosed NIDDM. Hanefeld, M., Fischer, S., Schmechel, H., Rothe, G., Schulze, J., Dude, H., Schwanebeck, U., Julius, U. Diabetes Care (1991) [Pubmed]
  3. Antiviral activity of antilipidemic compounds on herpes simplex virus type 1. Mehl, J.K., Witiak, D.T., Hamparian, V.V., Hughes, J.H. Antimicrob. Agents Chemother. (1980) [Pubmed]
  4. Clofibric acid down-regulation of metallothionein IIA in HepG2 human hepatoma cells. Bianchi, A., Bécuwe, P., Collet, P., Keller, J.M., Domenjoud, L., Dauça, M. Biochem. Pharmacol. (2002) [Pubmed]
  5. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Kliewer, S.A., Umesono, K., Noonan, D.J., Heyman, R.A., Evans, R.M. Nature (1992) [Pubmed]
  6. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Göttlicher, M., Widmark, E., Li, Q., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  7. Identification of cytosolic peroxisome proliferator binding protein as a member of the heat shock protein HSP70 family. Alvares, K., Carrillo, A., Yuan, P.M., Kawano, H., Morimoto, R.I., Reddy, J.K. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  8. Peroxisome proliferators induce apoptosis and decrease DNA synthesis in hepatoma cell lines. Goll, V., Viollon-Abadie, C., Nicod, L., Richert, L. Human & experimental toxicology. (2000) [Pubmed]
  9. UDP-glucuronosyltransferase-dependent bioactivation of clofibric acid to a DNA-damaging intermediate in mouse hepatocytes. Ghaoui, R., Sallustio, B.C., Burcham, P.C., Fontaine, F.R. Chem. Biol. Interact. (2003) [Pubmed]
  10. Aryloxoalcanoic compounds induce resistance to antibiotic therapy in urinary tract infection caused by Escherichia coli. Balagu??, C., St??rtz, N., Rey, R., Ruiz, C.S., Nader-Mac??as, M.E., Duffard, R., Duffard, A.M. FEMS Immunol. Med. Microbiol. (2006) [Pubmed]
  11. Studies with etofibrate in the rat. Part II: A comparison of the effects of prolonged and acute administration on plasma lipids, liver enzymes and adipose tissue lipolysis. Bocos, C., Castro, M., Quack, G., Herrera, E. Biochim. Biophys. Acta (1993) [Pubmed]
  12. Differential effects of altered hormonal state on the induction of acyl-CoA hydrolases and peroxisomal beta-oxidation by clofibric acid. Kawashima, Y., Katoh, H., Kozuka, H. Biochim. Biophys. Acta (1983) [Pubmed]
  13. Liver gene expression profiles of rats treated with clofibric acid: comparison of whole liver and laser capture microdissected liver. Michel, C., Desdouets, C., Sacre-Salem, B., Gautier, J.C., Roberts, R., Boitier, E. Am. J. Pathol. (2003) [Pubmed]
  14. The peroxisome proliferator-activated receptor mediates the induction of CYP4A6, a cytochrome P450 fatty acid omega-hydroxylase, by clofibric acid. Muerhoff, A.S., Griffin, K.J., Johnson, E.F. J. Biol. Chem. (1992) [Pubmed]
  15. Saliva and plasma levels and plasma protein binding of clofibrinic acid in uremic patients. Bjornsson, T.D., Meffin, P.J., Peters, F.A., Blaschke, T.F. Clin. Pharmacol. Ther. (1980) [Pubmed]
  16. Elevated 8-hydroxydeoxyguanosine in hepatic DNA of rats following exposure to peroxisome proliferators: relationship to carcinogenesis and nuclear localization. Cattley, R.C., Glover, S.E. Carcinogenesis (1993) [Pubmed]
  17. Characterization of ciprofibrate and clofibric acid as peroxisomal proliferators in primary cultures of rat hepatocytes. Feller, D.R., Singh, Y., Shirhatti, V.R., Kocarek, T.A., Liu, C.T., Krishna, G. Hepatology (1987) [Pubmed]
  18. Bezafibrate as differentiating factor of human myeloid leukemia cells. Scatena, R., Nocca, G., Sole, P.D., Rumi, C., Puggioni, P., Remiddi, F., Bottoni, P., Ficarra, S., Giardina, B. Cell Death Differ. (1999) [Pubmed]
  19. Stereospecificity of the chloride ion channel: the action of chiral clofibric acid analogues. Bettoni, G., Loiodice, F., Tortorella, V., Conte-Camerino, D., Mambrini, M., Ferrannini, E., Bryant, S.H. J. Med. Chem. (1987) [Pubmed]
  20. Keratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARalpha. Hanley, K., Jiang, Y., He, S.S., Friedman, M., Elias, P.M., Bikle, D.D., Williams, M.L., Feingold, K.R. J. Invest. Dermatol. (1998) [Pubmed]
  21. Peroxisome proliferator-binding protein: identification and partial characterization of nafenopin-, clofibric acid-, and ciprofibrate-binding proteins from rat liver. Lalwani, N.D., Alvares, K., Reddy, M.K., Reddy, M.N., Parikh, I., Reddy, J.K. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  22. Peroxisome proliferators enhance linoleic acid metabolism in rat liver. Increased biosynthesis of omega 6 polyunsaturated fatty acids. Kawashima, Y., Musoh, K., Kozuka, H. J. Biol. Chem. (1990) [Pubmed]
  23. Hypocholesterolemic and antiaggregatory properties of 2-hydroxytetronic acid redox analogues an their relationship to clofibric acid. Witiak, D.T., Kokrady, S.S., Patel, S.T., Huzoor Akbar, H., Feller, D.R., Newmann, H.A. J. Med. Chem. (1982) [Pubmed]
  24. Effect of some peroxisome proliferators on transforming growth factor-beta 1 gene expression and insulin-like growth factor II/mannose-6-phosphate receptor gene expression in rat liver. Rumsby, P.C., Davies, M.J., Price, R.J., Lake, B.G. Carcinogenesis (1994) [Pubmed]
  25. Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport. Wittmaack, F.M., Gåfvels, M.E., Bronner, M., Matsuo, H., McCrae, K.R., Tomaszewski, J.E., Robinson, S.L., Strickland, D.K., Strauss, J.F. Endocrinology (1995) [Pubmed]
  26. Peroxisome proliferator-activated receptor gamma1 (PPAR-gamma1) as a major PPAR in a tissue in which estrogen induces peroxisome proliferation. Ma, H., Tam, Q.T., Kolattukudy, P.E. FEBS Lett. (1998) [Pubmed]
  27. Human fatty acid omega-hydroxylase, CYP4A11: determination of complete genomic sequence and characterization of purified recombinant protein. Kawashima, H., Naganuma, T., Kusunose, E., Kono, T., Yasumoto, R., Sugimura, K., Kishimoto, T. Arch. Biochem. Biophys. (2000) [Pubmed]
  28. PPARalpha-dependent modulation of hepatic CYP1A by clofibric acid in rats. Shaban, Z., El-Shazly, S., Ishizuka, M., Kimura, K., Kazusaka, A., Fujita, S. Arch. Toxicol. (2004) [Pubmed]
  29. Expression of cytochrome P450 enzymes in hepatic organoid reconstructed by rat small hepatocytes. Miyamoto, S., Hirata, K., Sugimoto, S., Harada, K., Mitaka, T. J. Gastroenterol. Hepatol. (2005) [Pubmed]
  30. Elevated 8-hydroxydeoxyguanosine in hepatic DNA of rats following exposure to peroxisome proliferators: relationship to mitochondrial alterations. Sausen, P.J., Lee, D.C., Rose, M.L., Cattley, R.C. Carcinogenesis (1995) [Pubmed]
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