The C-DILI Assay is a novel in vitro method to evaluate a compound’s potential for cholestatic drug-induced liver injury (DILI).
The C-DILI Assay has demonstrated high in vitro – in vivo correlation with compounds known to have a risk for cholestatic hepatotoxicity. It is an effective tool for assessing the risk of cholestatic DILI and providing data useful in lead selection and managing toxicity risk.
The liver has multiple regulatory mechanisms that control the disposition of bile acids, including hepatic efflux, metabolism and synthesis. However if control mechanisms are disrupted, bile acid concentrations can reach a “tipping point” resulting in hepatotoxicity. The C-DILI Assay integrates compound effects including BSEP inhibition, inhibition of basolateral efflux by OSTs and / or MRP3/4, and FXR activation or antagonism, all of which impact the levels of bile acids in the liver, and provides a unique, clinically-predictive assessment of cholestasis risk.
We have develop assessment programs to investigate a compound's potential risk of causing cholestatic hepatotoxicity.