Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DuP-697 (5-bromo-2-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-thiophene), like celecoxib and rofecoxib, is a vicinal diaryl heterocycle highly selective cyclooxygenase-2 (COX-2) inhibitor. The aim of the study was to evaluate prenatal tolerability of DuP-697. The drug was administered orally in Tween 80 water suspension once a day to pregnant Wistar rats, on Days 7-18 of gestation. The initial dose, similar to the rat antipyretic dose, was set at 0.05 mg/kg. The middle dose, 3.5 mg/kg, corresponded to the rat anti-inflammatory and analgesic dose. The high dose was set at 35.0 mg/kg. Control animals received Tween 80 water suspension. On Day 21 of gestation, fetuses were delivered by laparotomy and double stained with alcian blue and alizarin red S or examined using the Wilson technique. Intrauterine growth retardation occurred in the groups exposed to the middle and highest dose of DuP-697. Minimal reactive and degenerative hepatic changes were found in both drug-exposed and control groups. Skeletal malformations were seen occasionally in all drug-treated and control groups. A significant increase in skeleton variations, such as delayed and asymmetrical ossification, was observed in fetuses exposed to the highest drug dose when compared with the control. These changes were not increased (P<0.1) in the middle drug-dose group. The experimentally-derived NOAEL for developmental toxicity was 0.05 mg/kg, and the corresponding LOAEL was 3.5 mg/kg.
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PMID:Prenatal effects of DuP-697-the irreversible, highly selective cyclooxygenase-2 inhibitor. 1284 52