Volixibat
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Volixibat
- DrugBank Accession Number
- DB13914
- Background
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 2. 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 pathogenesis1.
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 NASH3.
- Type
- Small Molecule
- Groups
- Experimental, Investigational
- Structure
- Weight
- Average: 805.96
Monoisotopic: 805.291416442 - Chemical Formula
- C38H51N3O12S2
- Synonyms
- Volixibat
- External IDs
- SHP626
Pharmacology
- Indication
Volixibat is an investigational drug that has not been approved for use in any conditions.
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- Pharmacodynamics
Not Available
- Mechanism of action
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 pathogenesis1.
Target Actions Organism AIleal sodium/bile acid cotransporter inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Volixibat potassium YWU8J6O8J0 1431935-92-0 CJMKTEIIPMBTJB-DXFHJFHKSA-M
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as hexoses. These are monosaccharides in which the sugar unit is a is a six-carbon containing moeity.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbohydrates and carbohydrate conjugates
- Direct Parent
- Hexoses
- Alternative Parents
- Benzothiepins / Monosaccharide sulfates / N-phenylureas / Benzylethers / Dialkylarylamines / Alkyl sulfates / Sulfuric acid monoesters / Oxanes / Sulfones / Ureas show 7 more
- Substituents
- Alcohol / Alkyl sulfate / Amine / Aromatic heteropolycyclic compound / Benzenoid / Benzothiepin / Benzylether / Carbonic acid derivative / Carbonyl group / Dialkyl ether show 23 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- X2JZ0451H8
- CAS number
- 1025216-57-2
- InChI Key
- ULVBLFBUTQMAGZ-RTNCXNSASA-N
- InChI
- InChI=1S/C38H51N3O12S2/c1-5-7-18-38(6-2)23-54(46,47)30-17-16-27(41(3)4)20-28(30)31(35(38)44)25-14-11-15-26(19-25)39-37(45)40-36-33(43)34(51-21-24-12-9-8-10-13-24)32(42)29(53-36)22-52-55(48,49)50/h8-17,19-20,29,31-36,42-44H,5-7,18,21-23H2,1-4H3,(H2,39,40,45)(H,48,49,50)/t29-,31-,32-,33-,34+,35-,36-,38-/m1/s1
- IUPAC Name
- {[(2R,3R,4S,5R,6R)-4-(benzyloxy)-6-[({3-[(3S,4R,5R)-3-butyl-7-(dimethylamino)-3-ethyl-4-hydroxy-1,1-dioxo-2,3,4,5-tetrahydro-1lambda6-benzothiepin-5-yl]phenyl}carbamoyl)amino]-3,5-dihydroxyoxan-2-yl]methoxy}sulfonic acid
- SMILES
- [H][C@@]1([C@@H](O)[C@](CC)(CCCC)CS(=O)(=O)C2=CC=C(C=C12)N(C)C)C1=CC=CC(NC(=O)N[C@@H]2O[C@H](COS(O)(=O)=O)[C@@H](O)[C@H](OCC3=CC=CC=C3)[C@H]2O)=C1
References
- General References
- Tiessen RG, Kennedy CA, Keller BT, Levin N, Acevedo L, Gedulin B, van Vliet AA, Dorenbaum A, Palmer M: 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. BMC Gastroenterol. 2018 Jan 5;18(1):3. doi: 10.1186/s12876-017-0736-0. [Article]
- Dawson PA: Role of the intestinal bile acid transporters in bile acid and drug disposition. Handb Exp Pharmacol. 2011;(201):169-203. doi: 10.1007/978-3-642-14541-4_4. [Article]
- Shire Pharmaceuticals - Newsroom Announcement [Link]
- External Links
- PubChem Compound
- 24987688
- PubChem Substance
- 347829333
- ChemSpider
- 35099493
- ChEMBL
- CHEMBL3707222
- Wikipedia
- Volixibat
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Recruiting Treatment Primary Bilary Cirrhosis (PBC) / Primary Biliary Cholangitis 1 somestatus stop reason just information to hide 2 Recruiting Treatment Primary Sclerosing Cholangitis (PSC) 1 somestatus stop reason just information to hide 2 Terminated Treatment Cholestasis of pregnancy 1 somestatus stop reason just information to hide 2 Terminated Treatment Steatohepatitis, Nonalcoholic 1 somestatus stop reason just information to hide 1 Completed Basic Science Steatohepatitis, Nonalcoholic 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.115 mg/mL ALOGPS logP 1.98 ALOGPS logP 2.88 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) -1.9 Chemaxon pKa (Strongest Basic) 2.23 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 221.26 Å2 Chemaxon Rotatable Bond Count 14 Chemaxon Refractivity 205.73 m3·mol-1 Chemaxon Polarizability 83.77 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine (PubMed:7592981, PubMed:9458785, PubMed:9856990). Transports various bile acids, unconjugated or conjugated, such as cholate and taurocholate (PubMed:7592981, PubMed:9458785, PubMed:9856990). Also responsible for bile acid transport in the renal proximal tubules, a salvage mechanism that helps conserve bile acids (Probable). Works collaboratively with the Na(+)-taurocholate cotransporting polypeptide (NTCP), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (PubMed:33222321)
- Specific Function
- bile acid
- Gene Name
- SLC10A2
- Uniprot ID
- Q12908
- Uniprot Name
- Ileal sodium/bile acid cotransporter
- Molecular Weight
- 37713.405 Da
References
- Tiessen RG, Kennedy CA, Keller BT, Levin N, Acevedo L, Gedulin B, van Vliet AA, Dorenbaum A, Palmer M: 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. BMC Gastroenterol. 2018 Jan 5;18(1):3. doi: 10.1186/s12876-017-0736-0. [Article]
Drug created at October 17, 2017 20:17 / Updated at February 21, 2021 18:54