The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies

Int J Mol Sci. 2021 Jan 14;22(2):784. doi: 10.3390/ijms22020784.

Abstract

The bile salt export pump (BSEP/ABCB11) is responsible for the transport of bile salts from hepatocytes into bile canaliculi. Malfunction of this transporter results in progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2) and intrahepatic cholestasis of pregnancy (ICP). Over the past few years, several small molecular weight compounds have been identified, which hold the potential to treat these genetic diseases (chaperones and potentiators). As the treatment response is mutation-specific, genetic analysis of the patients and their families is required. Furthermore, some of the mutations are refractory to therapy, with the only remaining treatment option being liver transplantation. In this review, we will focus on the molecular structure of ABCB11, reported mutations involved in cholestasis and current treatment options for inherited BSEP deficiencies.

Keywords: ABCB11; BRIC; BSEP; PFIC2; bile salts; chaperones; intrahepatic cholestasis.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 11 / metabolism
  • Animals
  • Bile Acids and Salts / metabolism*
  • Biological Transport
  • Cholestasis, Intrahepatic / drug therapy
  • Cholestasis, Intrahepatic / genetics*
  • Cholestasis, Intrahepatic / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Mutation*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / therapeutic use

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • Bile Acids and Salts
  • Small Molecule Libraries

Supplementary concepts

  • Cholestasis, progressive familial intrahepatic 2