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Liver-Activated Drug Lowers Cholesterol and Triglycerides

Drug targets thyroid hormone receptor without systemic side effects

FRIDAY, Sept. 21 (HealthDay News) -- A drug that targets the thyroid hormone receptor but is only activated in the liver lowers both cholesterol and triglycerides in rodents without the undesirable systemic side effects, according to a study published online Sept. 18 in the Proceedings of the National Academy of Sciences.

Mark Erion, Ph.D., and colleagues from Metabasis Therapeutics in La Jolla, Calif., characterized MB07811, a thyroid hormone receptor agonist and prodrug that was activated only in the liver by two liver enzymes.

Pharmacokinetic studies in rats showed that MB07811 targeted the liver and spared the heart and other tissues, and its active form was rapidly eliminated in the bile. In diet-induced obese mice, MB07811 reduced cholesterol and both serum and hepatic triglycerides, unlike a similar compound that was not targeted to the liver.

"These results indicate that targeting thyroid hormone receptor agonists to the liver has the potential to lower both cholesterol and triglyceride levels with an acceptable safety profile," Erion and colleagues conclude.

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