Intestinal toxicity in rats following administration of CDK4/6 inhibitors is independent of primary pharmacology

Male Sprague Dawley rats (CRL/CD SD, Charles River Laboratories, Hollister, CA) 6-8 weeks-old were utilized. We used microarrays to analyze changes in gene expression in gastrointestinal tissue (musocal scrapings) after 4 days of dosing. Total RNA was extracted from tissues of 3 rats per experimental group for analysis. Ten rats per group were administered vehicle (0.5% methyl cellulose), abemaciclib (36 or 120 mg/kg/day), palbociclib (30 or 100 mg/kg/day), or ribociclib (300 mg/kg/day) via oral gavage for 4 or 15 days. The vehicle for abemaciclib and ribociclib was 0.5% hydroxypropyl methylcellulose, 0.25% tween 80 in 10 mM citrate buffer, pH3; and the vehicle for palbociclib was 0.5% methylcellulose.