Investigational Drug Details
| Drug ID: | D332 |
| Drug Name: | Volixibat |
| Synonyms: | Volixibat potassium; Volixibat; SHP626 |
| Type: | Chemical drug |
| DrugBank ID: | DB13914 |
| DrugBank Description: | Volixibat, also known as SHP626 or LUM002, is an investigational drug that will potentially be used for the treatment of Non-Alcoholic Steatohepatitis (NASH). If approved for use, it will be the first available agent for the treatment of NASH. Volixibat is a selective inhibitor of the apical sodium-dependent bile acid transporter (ASBT), a transmembrane protein primarily expressed by enterocytes of the ileum. Also known as the ileal bile acid transporter (IBAT), ASBT is primarily responsible for the enterohepatic recirculation of bile acids and ultimately for hepatic lipid and glucose metabolism . Inhibiting this enzyme results in a decrease of bile acids returning to the liver, which is helpful for the treatment of NASH as abnormal cholesterol metabolism and accumulation of free cholesterol in the liver have been implicated in its pathogenesis. According to Shire, the pharmaceutical manufacturer of Volixibat, it has been granted fast track status by the Food and Drug Administration due to promising initial results and a need for therapeutic treatments for NASH. |
| PubChem ID: | -- |
| CasNo: | 1025216-57-2 |
| Repositioning for NAFLD: | No |
| SMILES: | O[C@@H]1[C@@H](c2c(S(=O)(=O)C[C@]1(CCCC)CC)ccc(c2)N(C)C)c1cc(NC(=O)N[C@H]2[C@H](O)[C@@H](OCc3ccccc3)[C@@H]([C@H](O2)COS(=O)(=O)O)O)ccc1 |
| Structure: |
|
| InChiKey: | ULVBLFBUTQMAGZ-RTNCXNSASA-N |
| Molecular Weight: | 805.969 |
| DrugBank Targets: | Ileal sodium/bile acid cotransporter inhibitor |
| DrugBank MoA: | Volixibat is a selective inhibitor of the apical sodium-dependent bile acid transporter (ASBT), a transmembrane protein primarily expressed by enterocytes of the ileum. ASBT is primarily responsible for the recirculation of bile acids and therefore for hepatic lipid and glucose metabolism. Inhibiting this enzyme results in a decrease of bile acids returning to the liver, which is helpful for the treatment of NASH as abnormal cholesterol metabolism and accumulation of free cholesterol in the liver have been implicated in its pathogenesis. |
| DrugBank Pharmacology: | -- |
| DrugBank Indication: | Volixibat is an investigational drug that has not been approved for use in any conditions. |
| Targets: | SLC10A2 inhibitor; ASBT inhibitor |
| Therapeutic Category: | Lipid regulating agents |
| Clinical Trial Progress: | Phase 3 terminated (NCT02787304: Volixibat did not reduce the amount of fat in the liver, nor did it have any other beneficial effect on liver injury. Participants in the study generally tolerated the side effects of volixibat and, as in previous studies, the main side effect was diarrhoea. These results show that volixibat is not an effective treatment for people with fatty liver disease.) |
| Latest Progress: | Failed in clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0193 | NCT02787304 | Phase 2 | Terminated | Has Results | October 24, 2016 | November 25, 2019 | Details |
| L0332 | NCT02287779 | Phase 1 | Completed | Has Results | January 19, 2015 | March 26, 2019 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A08135 | 32234329 | J Hepatol | Volixibat in adults with non-alcoholic steatohepatitis: 24-week interim analysis from a randomized, phase II study. | Details |
| A10698 | 31233523 | PLoS One | Apical sodium-dependent bile acid transporter inhibition with volixibat improves metabolic aspects and components of non-alcoholic steatohepatitis in Ldlr-/-.Leiden mice. | Details |
| A14180 | 29548345 | BMC Pharmacol Toxicol | A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis. | Details |
| A14659 | 29304731 | BMC Gastroenterol | Safety, tolerability and pharmacodynamics of apical sodium-dependent bile acid transporter inhibition with volixibat in healthy adults and patients with type 2 diabetes mellitus: a randomised placebo-controlled trial. | Details |
| A47940 | 28702877 | Eur J Drug Metab Pharmacokinet | Absorption, Distribution, Metabolism, and Excretion of [14C]-Volixibat in Healthy Men: Phase 1 Open-Label Study. | Details |