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Chemical Compound Review

Alond     2-[4-oxo-3-[[5- (trifluoromethyl)benzothiaz...

Synonyms: Xedia, ZOPOLRESTAT, Zopolrestatum, CHEMBL10372, SureCN49012, ...
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Disease relevance of ZOPOLRESTAT


High impact information on ZOPOLRESTAT


Chemical compound and disease context of ZOPOLRESTAT


Biological context of ZOPOLRESTAT


Anatomical context of ZOPOLRESTAT


Associations of ZOPOLRESTAT with other chemical compounds

  • Potent, orally active aldose reductase inhibitors related to zopolrestat: surrogates for benzothiazole side chain [15].
  • Using a fluorometric assay, it was determined that zopolrestat, an acetic acid-type inhibitor, bound to aldose reductase complexed with either NADPH or NADP+ [16].
  • The enzyme mutant W20A severely affected the inhibitory potencies of a variety of commercially developed aldose reductase inhibitors (zopolrestat, tolrestat, FK366, AL1576, alrestatin, ponalrestat, and sorbinil) [17].
  • Our findings show that zopolrestat restored the hyporesponsiveness of diabetic rats to antigen provocation, in parallel with impairment of alloxan-induced mast cell depletion and hypercorticolism, indicating that polyol pathway activity seems to play an important role in these phenomena [12].
  • Consistent with molecular models, the inhibitory activity of Tolrestat, Sorbinil and Zopolrestat decreased 800-2000-fold when tested with the mutant enzyme in which Trp20 was replaced with alanine [18].

Gene context of ZOPOLRESTAT

  • We have determined the 1.7 A resolution structure of the FR-1 in a ternary complex with NADPH and zopolrestat, a potent aldose reductase inhibitor [19].
  • These increments were attenuated by zopolrestat, an AR inhibitor [20].
  • There were significantly fewer CD31-positive vessels perfield in both groups treated with zopolrestat compared to the infusion-only group: group 2, 9 (7 - 12); group 3, 17 (13 - 38), compared to group 1, 37 (32 - 39), p < 0.05 [21].
  • These data suggest that glycolytic flux in diabetic hearts is inhibited at glyceraldehyde-3-phosphate dehydrogenase and that inhibition of the polyol pathway with zopolrestat increases glycolytic flux in these hearts [22].
  • The AGE-induced enhancement in TGF-beta1 and type IV collagen expression were suppressed by either zopolrestat or transfection with an AR antisense oligonucleotide [20].

Analytical, diagnostic and therapeutic context of ZOPOLRESTAT


  1. Aldose reductase functions as a detoxification system for lipid peroxidation products in vasculitis. Rittner, H.L., Hafner, V., Klimiuk, P.A., Szweda, L.I., Goronzy, J.J., Weyand, C.M. J. Clin. Invest. (1999) [Pubmed]
  2. Aldose reductase inhibition protects diabetic and nondiabetic rat hearts from ischemic injury. Ramasamy, R., Oates, P.J., Schaefer, S. Diabetes (1997) [Pubmed]
  3. Effect of sorbitol dehydrogenase inhibition on experimental diabetic autonomic neuropathy. Schmidt, R.E., Dorsey, D.A., Beaudet, L.N., Plurad, S.B., Williamson, J.R., Ido, Y. J. Neuropathol. Exp. Neurol. (1998) [Pubmed]
  4. Pharmacokinetics of the aldose reductase inhibitor, zopolrestat, in humans. Inskeep, P.B., Ronfeld, R.A., Peterson, M.J., Gerber, N. Journal of clinical pharmacology. (1994) [Pubmed]
  5. Zopolrestat prevention of proteinuria, albuminuria and cataractogenesis in diabetes mellitus. Beyer-Mears, A., Mistry, K., Diecke, F.P., Cruz, E. Pharmacology (1996) [Pubmed]
  6. Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat. Wilson, D.K., Tarle, I., Petrash, J.M., Quiocho, F.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  7. The response of antioxidant genes to hyperglycemia is abnormal in patients with type 1 diabetes and diabetic nephropathy. Hodgkinson, A.D., Bartlett, T., Oates, P.J., Millward, B.A., Demaine, A.G. Diabetes (2003) [Pubmed]
  8. Molecular modeling of the aldose reductase-inhibitor complex based on the X-ray crystal structure and studies with single-site-directed mutants. Singh, S.B., Malamas, M.S., Hohman, T.C., Nilakantan, R., Carper, D.A., Kitchen, D. J. Med. Chem. (2000) [Pubmed]
  9. Bioavailability, multiple-dose pharmacokinetics, and biotransformation of the aldose reductase inhibitor zopolrestat in dogs. Schneider, R.P., Davenport, C.J., Hoffmaster, K.A., Inskeep, P.B. Drug Metab. Dispos. (1998) [Pubmed]
  10. Tissue distribution and biotransformation of zopolrestat, an aldose reductase inhibitor, in rats. Schneider, R.P., Fouda, H.G., Inskeep, P.B. Drug Metab. Dispos. (1998) [Pubmed]
  11. Pharmacokinetics of zopolrestat, a carboxylic acid aldose reductase inhibitor, in normal and diabetic rats. Inskeep, P.B., Reed, A.E., Ronfeld, R.A. Pharm. Res. (1991) [Pubmed]
  12. Aldose reductase inhibitor zopolrestat restores allergic hyporesponsiveness in alloxan-diabetic rats. Carvalho, V.F., Barreto, E.O., Serra, M.F., Cordeiro, R.S., Martins, M.A., Fortes, Z.B., E Silva, P.M. Eur. J. Pharmacol. (2006) [Pubmed]
  13. Intracellular mechanism of high D-glucose-induced modulation of vascular cell proliferation. Graier, W.F., Grubenthal, I., Dittrich, P., Wascher, T.C., Kostner, G.M. Eur. J. Pharmacol. (1995) [Pubmed]
  14. Aldose reductase inhibition restores endothelial cell function in diabetic rabbit aorta. Tesfamariam, B., Palacino, J.J., Weisbrod, R.M., Cohen, R.A. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
  15. Potent, orally active aldose reductase inhibitors related to zopolrestat: surrogates for benzothiazole side chain. Mylari, B.L., Beyer, T.A., Scott, P.J., Aldinger, C.E., Dee, M.F., Siegel, T.W., Zembrowski, W.J. J. Med. Chem. (1992) [Pubmed]
  16. Kinetic and spectroscopic evidence for active site inhibition of human aldose reductase. Nakano, T., Petrash, J.M. Biochemistry (1996) [Pubmed]
  17. Mechanism of aldose reductase inhibition: binding of NADP+/NADPH and alrestatin-like inhibitors. Ehrig, T., Bohren, K.M., Prendergast, F.G., Gabbay, K.H. Biochemistry (1994) [Pubmed]
  18. Probing the inhibitor-binding site of aldose reductase with site-directed mutagenesis. Hohman, T.C., El-Kabbani, O., Malamas, M.S., Lai, K., Putilina, T., McGowan, M.H., Wane, Y.Q., Carper, D.A. Eur. J. Biochem. (1998) [Pubmed]
  19. 1.7 A structure of FR-1, a fibroblast growth factor-induced member of the aldo-keto reductase family, complexed with coenzyme and inhibitor. Wilson, D.K., Nakano, T., Petrash, J.M., Quiocho, F.A. Biochemistry (1995) [Pubmed]
  20. Interaction between the polyol pathway and non-enzymatic glycation on mesangial cell gene expression. Dan, Q., Wong, R.L., Yin, S., Chung, S.K., Chung, S.S., Lam, K.S. Nephron Exp. Nephrol. (2004) [Pubmed]
  21. Effects of inhibition of the polyol pathway during chronic peritoneal exposure to a dialysis solution. van Westrhenen, R., Aten, J., Aberra, M., Dragt, C.A., Deira, G., Krediet, R.T. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. (2005) [Pubmed]
  22. Aldose reductase inhibition improves altered glucose metabolism of isolated diabetic rat hearts. Trueblood, N., Ramasamy, R. Am. J. Physiol. (1998) [Pubmed]
  23. Synthesis, activity, and molecular modeling of new 2, 4-dioxo-5-(naphthylmethylene)-3-thiazolidineacetic acids and 2-thioxo analogues as potent aldose reductase inhibitors. Fresneau, P., Cussac, M., Morand, J.M., Szymonski, B., Tranqui, D., Leclerc, G. J. Med. Chem. (1998) [Pubmed]
  24. Can diabetic neuropathy be prevented by angiotensin-converting enzyme inhibitors? Malik, R.A. Ann. Med. (2000) [Pubmed]
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