Glycerol phenylbutyrate as an effective chemical chaperone for traffic-defective ABCB4 variants: comparative analysis with 4-phenylbutyrate
Year: 2026
Type: article
Abstract: The ABCB4 transporter is localised at the canalicular membrane of hepatocytes, where it mediates the secretion of phosphatidylcholine into bile. Genetic variations in the ABCB4 gene are responsible for rare cholestatic liver diseases of varying severity, the most severe form being progressive familial intrahepatic cholestasis type 3. Existing treatments do not cure most patients with this disease, who require liver transplantation before adulthood. Consequently, there is a need to develop alternative pharmacological therapies. 4-phenylbutyrate and glycerol phenylbutyrate can partially correct the mistrafficking of endoplasmic reticulum-retained ABCB11 variants, thereby improving the clinical condition of patients with ABCB11 deficiency, but in vitro and in vivo data on ABCB4 are limited. In this study, we tested the ability of these two chemical chaperones to rescue traffic-defective ABCB4 variants in vitro by assessing their effects on subcellular localisation and phospholipid efflux capability, which revealed a greater rescuing capacity of glycerol phenylbutyrate over 4-phenylbutyrate. However, the non-equimolar doses used here preclude a direct comparison of the relative efficacy of the two molecules.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,990
OpenAlex ID: W7225745865