elobixibat   Click here for help

GtoPdb Ligand ID: 9996

Synonyms: 2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1λ6,5-benzothiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]acetic acid | A3309 | AJG533 | AZD-7806 | AZD7806 | Goofice®
Approved drug
elobixibat is an approved drug (Japan (2018))
Compound class: Synthetic organic
Comment: Elobixibat is an orally available inhibitor of the ileal bile acid transporter (IBAT or ASBT), which is the protein product of the SLC10A2 gene. It is being evaluated for clinical utility in the management of chronic constipation [1,3,6]. The chemical structure is claimed as Example 14 in Albireo Ab's patent US20130225511A1 [2] (we have chosen this iteration of the patent as it has both chemical structure images and data included in online versions).
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 18
Topological polar surface area 175.79
Molecular weight 695.27
XLogP 7.58
No. Lipinski's rules broken 2
Click here for help
Canonical SMILES CCCCC1(CCCC)CN(c2ccccc2)c2c(S(=O)(=O)C1)cc(c(c2)SC)OCC(=O)NC(c1ccccc1)C(=O)NCC(=O)O
Isomeric SMILES CCCCC1(CCCC)CN(c2ccccc2)c2c(S(=O)(=O)C1)cc(c(c2)SC)OCC(=O)N[C@H](c1ccccc1)C(=O)NCC(=O)O
InChI InChI=1S/C36H45N3O7S2/c1-4-6-18-36(19-7-5-2)24-39(27-16-12-9-13-17-27)28-20-30(47-3)29(21-31(28)48(44,45)25-36)46-23-32(40)38-34(26-14-10-8-11-15-26)35(43)37-22-33(41)42/h8-17,20-21,34H,4-7,18-19,22-25H2,1-3H3,(H,37,43)(H,38,40)(H,41,42)/t34-/m1/s1
No information available.
Summary of Clinical Use Click here for help
Elobixibat is approved in Japan (trade name Goofice®) for the treatment of chronic constipation. Phase 3 clinical trial results from Japanese studies are published in [4] and [5]. Elobixibat was found to be effective in resolving constipation and was well tolerated in the short- and long-term.
Elobixibat was also investiagted in nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), with the hypothesis being that ASBT inhibition might improve the liver damage (scarring and inflammation) and disordered levels of bile acids, fat and glucose, in these conditions.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Elobixibat increases intracolonic concentrations of endogenous bile acids and subsequently enhances colonic secretion and improves gut motility [1].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04235205 Efficacy and Safety of Elobixibat in Combination With Cholestyramine for Nonalcoholic Fatty Liver Disease Phase 2 Interventional Yokohama City University
NCT01038687 Effect of Ileal Bile Acid Transporter Inhibitor in Functional Constipation Phase 2 Interventional Mayo Clinic
NCT04006145 A Phase 2 Study of Elobixibat in Adults With NAFLD or NASH Phase 2 Interventional Albireo Albireo terminated development of elobixibat for NASH and NAFLD, as no improvement in liver enzyme levels or reduction in liver fat that would suggest clinical benefit in NASH, was detected by this trial.