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Chemical Compound Review:

LUFIRONIL N,N'-bis(2- methoxyethyl)pyridine-2,4...

Synonyms: Lufironilo, Lufironilum, Hoe-077, SureCN344625, CHEMBL2106793, ...

Matsumura, Y. et al., Bickel, M. et al., Sakaida, I. et al., Sakaida, I. et al., Wang, Y.J. et al., et al.

Okita, Sakaida, Hino,

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Disease relevance of HOE 077

The effect of a newly synthesized prolyl4-hydroxylase (PH) inhibitor, HOE 077 (pyridine-2, 4-di-carboxylic-di(2-methoxyethyl)amide), was examined using the model of choline-deficient L-amino acid (CDAA) defined diet-induced liver fibrosis in 16-week-old male Wistar rats [1].
They show HOE 077 to be a promising agent for the inhibition of hepatic fibrosis [2].

High impact information on HOE 077

They were no more effective in co-cultures containing hepatocytes than in pure stellate cell cultures, indicating that metabolic conversion of HOE 077 was not required [3].
The concurrent administration of HOE 077 reduced the number, average diameter and percent area of GSTP-positive lesions in a dose-dependent manner, in parallel with the reduction in hydroxyproline content [4].
S 0885 and HOE 077 inhibit CCl4-induced liver fibrosis in rats, as shown by significantly reduced hydroxyproline content of the liver and improved liver histology [5].
Pharmacokinetics and metabolism of HOE 077. Preclinical studies [6].
HOE 077 is well absorbed from the gastrointestinal tract [5].

Chemical compound and disease context of HOE 077

BACKGROUND/AIMS: The aim of this study was to investigate the effect and mechanism of fibrosuppression by a newly synthesized prolyl 4-hydroxylase inhibitor [HOE 077, 2, 4-pyridine dicarboxylic acid bis [(2-methoxyethyl) amide]] on pig serum-induced liver fibrosis in the rat [7].

Biological context of HOE 077

General pharmacology, toxicology and future clinical development of HOE 077 [8].
Prolyl 4-hydroxylase inhibitor (HOE 077) prevents TIMP-1 gene expression in rat liver fibrosis [9].

Anatomical context of HOE 077

At a concentration of 1 mM, HOE 077 does not affect collagen synthesis in human fibroblasts, bovine chondrocytes and chicken calvaria [5].
We have investigated whether a potent prolyl 4-hydroxylase inhibitor (HOE-077) can influence the deposition of extracellular matrix in the pancreas [10].

Gene context of HOE 077

We have demonstrated that antifibrotic agents, such as HOE 077, TJ-9 and interferon, can reduce the risk of HCC [11].

Analytical, diagnostic and therapeutic context of HOE 077

Electron microscopy revealed that 200 ppm of HOE 077 prevented the loss of fat droplets [7].
HOE 077 wa rapidly and completely absorbed after oral administration [6].

References

The prolyl 4-hydroxylase inhibitor HOE 077 prevents activation of Ito cells, reducing procollagen gene expression in rat liver fibrosis induced by choline-deficient L-amino acid-defined diet. Sakaida, I., Matsumura, Y., Kubota, M., Kayano, K., Takenaka, K., Okita, K. Hepatology (1996) [Pubmed]
Fibrosis of the liver in rats induced by bile duct ligation. Effects of inhibition by prolyl 4-hydroxylase. Böker, K., Schwarting, G., Kaule, G., Günzler, V., Schmidt, E. J. Hepatol. (1991) [Pubmed]
Two novel antifibrotics, HOE 077 and Safironil, modulate stellate cell activation in rat liver injury: differential effects in males and females. Wang, Y.J., Wang, S.S., Bickel, M., Guenzler, V., Gerl, M., Bissell, D.M. Am. J. Pathol. (1998) [Pubmed]
Prevention of fibrosis reduces enzyme-altered lesions in the rat liver. Sakaida, I., Kubota, M., Kayano, K., Takenaka, K., Mori, K., Okita, K. Carcinogenesis (1994) [Pubmed]
Beneficial effects of inhibitors of prolyl 4-hydroxylase in CCl4-induced fibrosis of the liver in rats. Bickel, M., Baader, E., Brocks, D.G., Engelbart, K., Günzler, V., Schmidts, H.L., Vogel, G.H. J. Hepatol. (1991) [Pubmed]
Pharmacokinetics and metabolism of HOE 077. Preclinical studies. Kellner, H.M., Volz, M., Badder, E., Kürzel, G.U., Eckert, H.G. J. Hepatol. (1991) [Pubmed]
Prolyl 4-hydroxylase inhibitor (HOE 077) inhibits pig serum-induced rat liver fibrosis by preventing stellate cell activation. Matsumura, Y., Sakaida, I., Uchida, K., Kimura, T., Ishihara, T., Okita, K. J. Hepatol. (1997) [Pubmed]
General pharmacology, toxicology and future clinical development of HOE 077. Horn, W. J. Hepatol. (1991) [Pubmed]
Prolyl 4-hydroxylase inhibitor (HOE 077) prevents TIMP-1 gene expression in rat liver fibrosis. Sakaida, I., Uchida, K., Hironaka, K., Okita, K. J. Gastroenterol. (1999) [Pubmed]
Failure of a prolyl 4-hydroxylase inhibitor to alter extracellular matrix deposition during experimental pancreatitis. Weidenbach, H., Lerch, M.M., Turi, S., Bachem, M., Adler, G. Digestion (1997) [Pubmed]
Current strategies for chemoprevention of hepatocellular carcinoma. Okita, K., Sakaida, I., Hino, K. Oncology (2002) [Pubmed]

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