5 Day Oral Study of A-998679 in Male Sprague Dawley Rats (liver)

Male Sprague-Dawley rats [Crl:CD(SD)IGS BR], weighing ~250 g at study initiation were obtained from Charles River Laboratories, Inc. (Wilmington, MA). Rats were housed singly in ventilated, stainless steel, wire-bottom hanging cages and fed non-certified Rodent Chow (Harlan Labs, Madison, WI) and water ad libitum and acclimated for at least 5 days after arrival. Rats were randomly assigned to various treatment groups (3 rats/group) and were dosed once daily by oral gavage with vehicle (0.2% hydroxypropylmethylcellulose at a dose volume of 10 ml/kg) or with 30, 100, or 200 mg/kg of A-998679. All rats were fasted overnight after their last dose, weighed and sacrificed under isoflurane anesthesia. Liver and small intestine (jejunum) were flash frozen in liquid nitrogen and stored at 80C until processing for gene expression profiling on the Affymetrix platform.

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Liguori MJ, Lee CH, Liu H, Ciurlionis R, Ditewig AC, Doktor S, Andracki ME, Gagne GD, Waring JF, Marsh KC, Gopalakrishnan M, Blomme EA, Yang Y