BioIVT research links BSEP inhibition with bile acid suppression in DILI
BioIVT announced results of their research into cholestatic drug-induced liver injury and the BSEP bile acid transporter, according to a press release.
The data showed that BSEP inhibition triggers the activation of compensatory mechanisms that suppress bile acid synthesis and increase bile acid excretion through routes other than BSEP.
“Cholestatic DILI is known to have a weak association with BSEP inhibition,” Jonathan Jackson, PhD, BioIVT study director and lead author, said in the release. “Our study demonstrated the ‘link’ between BSEP inhibition and [farnesoid X receptor (FXR)], a master regulator of bile acid homeostasis. FXR activation by BSEP inhibition may explain the weak concordance between BSEP inhibition potency and cholestatic DILI incidence.”
BioIVT also announced that its C-DILI Assay was able to integrate cellular compensatory mechanisms with BSEP inhibition.
“Our discovery suggests a new paradigm is required to accurately predict a drug candidate’s cholestatic DILI potential, and new methods are needed, such as our C-DILI Assay,” Jackson said in the release.