Quantitative Systems Toxicology Identifies the Mechanism and Data Gaps for Evaluating the Hepatotoxicity of Compound V

Authors: Lakhani VV, Generaux GT, Siler SQ, Howell B, Woodhead JL
Conference: SLP MIDD+
Keywords: Compound V, FIH/Phase I, hepatocytes, hepatotoxicity, in silico, in vitro, liver, QST, SLP2021MIDD
Software: GastroPlus®
Division: Quantitative Systems Pharmacology (QSP)

Purpose

Compound V is a small molecule with potential therapeutic benefits in patients with obesity. An early clinical safety trial produced two patients with liver enzyme elevations. Using a combination of in vitro assays and in silico modeling, this study investigated whether Compound V is capable of inducing hepatocyte cell death, and if so, what mechanism(s) may be involved and to what extent the compound concentration in the liver plays a role.

By Vinal V. Lakhani, Grant Generaux, Scott Q. Siler, Brett A. Howell, Jeffrey L. Woodhead

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Presented at SLP MIDD+ Virtual Conference March 3-4, 2021