PD-166793 is a potent, selective, orally active, pan-MMP inhibitor with IC50 values of 4, 7, and 8 nM for MMP-2, MMP-3, and MMP-13, respectively, and 6.0, 7.2, and 7.9 μM for MMP-1, -7, and -9, respectively. PD-166793 reduces left ventricular remodeling and dysfunction in rat models of progressive heart failure[1][2][3].PD-166793 inhibited AMPD activity in rat heart homogenates by 20% at a concentration of 0.1 μM, and significantly reduced MMP-9 activity in normal human cardiac fibroblasts at a concentration of 100 μM for 36 h[2].
PD-166793 动物研究
Animal study
At a dose of 1 mg/kg/day administered by gavage daily for 10 weeks, PD-166793 largely prevented the adverse remodelling commonly seen in the aortocaval (AV) fistula model[3].Administered orally at a dose of 5 mg/kg, PD-166793 exhibited excellent pharmacokinetics in rats with a t1/2 of 43.6 hours, Cmax of 42.4 μg/mL, and an AUC0-∞ of 2,822 μg/hour/mL[1].Administered daily by gavage at a dose of 1 mg/kg, starting 2 weeks before surgery and continuing until 8 weeks after surgery, PD-166793 prevents ventricular dilatation and attenuates typical hypertrophy caused by chronic volume overload in animals[3].
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