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Mar 12, 2018
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Prediction of the Liver Toxicity of the Endothelin Receptor Antagonists Sitaxsentan and Ambrisentan for the Treatment of Pulmonary Arterial Hypertension with a Quantitative Systems Toxicology Tool (DILIsym)

Introduction

  • Sitaxsentan and ambrisentan are highly selective endothelin-1 type A receptor antagonists which were developed for the treatment of pulmonary arterial hypertension
  • Sitaxsentan was voluntarily withdrawn from the market due to concerns about liver toxicity, whereas ambrisentan is currently on the market
  • DILIsym, a mathematical framework of drug-induced liver toxicity, was used for quantitative system toxicology (QST) studies of the compounds
  • It is important to ensure that QST tools are capable of distinguishing between toxic and non-toxic compounds

Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas

By Brett A. Howell, Scott Q. Siler

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