Volixibat

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

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
Thumb
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.

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
AIleal sodium/bile acid cotransporter
inhibitor
Humans
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
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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

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Product Ingredients
IngredientUNIICASInChI Key
Volixibat potassiumYWU8J6O8J01431935-92-0CJMKTEIIPMBTJB-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
  1. 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]
  2. 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]
  3. Shire Pharmaceuticals - Newsroom Announcement [Link]
PubChem Compound
24987688
PubChem Substance
347829333
ChemSpider
35099493
ChEMBL
CHEMBL3707222
Wikipedia
Volixibat

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingTreatmentIntrahepatic Cholestasis of Pregnancy1
2RecruitingTreatmentPrimary Sclerosing Cholangitis (PSC)1
2TerminatedTreatmentNonalcoholic Steatohepatitis1
1CompletedBasic ScienceNonalcoholic Steatohepatitis1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentNonalcoholic Steatohepatitis1

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
PropertyValueSource
Water Solubility0.115 mg/mLALOGPS
logP1.98ALOGPS
logP2.88ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)-1.9ChemAxon
pKa (Strongest Basic)2.23ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area221.26 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity205.73 m3·mol-1ChemAxon
Polarizability83.77 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Bile acid:sodium symporter activity
Specific Function
Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism.
Gene Name
SLC10A2
Uniprot ID
Q12908
Uniprot Name
Ileal sodium/bile acid cotransporter
Molecular Weight
37713.405 Da
References
  1. 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 on October 17, 2017 20:17 / Updated on February 21, 2021 18:54