XL-784

Animal experiment:

Mice[2]A total of 89 mice undergo aortic perfusion. Beginning the day of perfusion, animals are treated with the study drug (e.g., XL-784), a negative control, or doxycycline. 76 animals survive to sacrifice and are included in the analysis. Animals treated with the experimental agent, XL-784, receive gavage daily with the agent diluted in 0.1 mL of Cremophor, a nonionic castor oil-based solubilizer and emulsifying agent. Three doses of the drug are used, 50 (n=17), 125 (n=17), and 250 mg/kg per d (n=18) administered as a single daily dose. The fifth group of mice do not receive a gavage treatment but are treated with doxycycline (n=19) in their drinking water at a concentration 100 mg/kg per d of the animals. In the second treatment protocol, a total of 50 animals underwent aortic perfusion and 47 animals survive for analysis at 14 days. The 5 treatment groups are XL-784 at 250, 375, or 500 mg/kg, Cremaphor diluent alone, or doxycycline 100 mg/kg. Animals are assigned in groups of 3 to a treatment group rotating randomly through each treatment group until there are 9 animals in each group except for the 500 mg/kg per d group which totaled to 14 animals[2].

References:

[1]. Williams JM, et al. Evaluation of metalloprotease inhibitors on hypertension and diabetic nephropathy. Am J Physiol Renal Physiol. 2011 Apr;300(4):F983-98.
[2]. Ennis T, et al. Effect of novel limited-spectrum MMP inhibitor XL784 in abdominal aortic aneurysms. J Cardiovasc Pharmacol Ther. 2012 Dec;17(4):417-26.