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