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Identification
NameVedolizumab
Accession NumberDB09033
TypeBiotech
GroupsApproved
Description

Vedolizumab is a recombinant humanized IgG1 monoclonal antibody directed against the human lymphocyte α4β7 integrin, a key mediator of gastrointestinal inflammation. It is used in the treatment of moderate to severe active ulcerative colitis and Crohn’s disease for patients who have had an inadequate response with, lost response to, or were intolerant to inhibitors of tumor necrosis factor-alpha (TNF-alpha) or other conventional therapies. By blocking its primary target, α4β7 integrin, vedolizumab reduces inflammation in the gut. Vedolizumab is administered by IV infusion over a period of 30 minutes; after the first dose, it is given again at two and six weeks and then every 8 weeks thereafter.

Protein structureDb09033
Related Articles
Protein chemical formulaC6528H10072N1732O2042S42
Protein average weight146837.0 Da
Sequences
>Heavy Chain Sequence
QVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYWMHWVRQAPGQRLEWIGEIDPSESNTNY
NQKFKGRVTLTVDISASTAYMELSSLRSEDTAVYYCARGGYDGWDYAIDYWGQGTLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELAG
APSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY
NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD
ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR
WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light Chain Sequence
DVVMTQSPLSLPVTPGEPASISCRSSQSLAKSYGNTYLSWYLQKPGQSPQLLIYGISNRF
SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCLQGTHQPYTFGQGTKVEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
Entyvio
External Identifiers
  • LDP 02
  • LDP-02
  • LDP02
  • MLN-0002
  • MLN-02
  • MLN0002
  • MLN02
  • UNII-9RV78Q2002
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Entyvioinjection, powder, lyophilized, for solution300 mg/5mLintravenousTakeda Pharmaceuticals America, Inc.2014-05-20Not applicableUs
Entyviopowder for solution300 mgintravenousTakeda Canada Inc2015-04-21Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII9RV78Q2002
CAS number943609-66-3
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationVedolizumab is indicated for adult patients with moderately to severely active UC or CD who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids.
PharmacodynamicsNon-clinical studies have shown that the pharmacodynamic effects of vedolizumab are reversible upon removal of the antibody: pharmacologic activity of cells inhibited by vedolizumab could be partially restored within 24 hours after removal, with near complete restoration within 4 days. There are no known drug interactions as vedolizumab is a humanized antibody and does not modulate production of cytokines, which is known to affect drug metabolism.
Mechanism of actionVedolizumab binds to α4β7 integrin, a key mediator of gastrointestinal inflammation expressed on the surfaces of T and B lymphocytes. By selectively inhibiting the α4β7 integrin, vedolizumab inhibits adhesion of lymphocytes to its natural ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thereby preventing lymphocytic cells from entering the gut lamina propria and gut-associated lymphoid tissue (GALT). Specifically inhibiting this pathway alleviates GI inflammation without impairing systemic immune responses.
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AbsorptionThe intended route of administration is intravenous, therefore there is no absorption data and bioavailability is expected to be 100%.
Volume of distribution

Serum apparent volume of distribution at steady-state has been found to be moderately greater than the serum volume. It is therefore expected to be confined to the systemic circulation, as expected for a high molecular weight protein.

Protein bindingVedolizumab binds specifically to α4β7 integrin but does not bind to, or inhibit function of, α4β1 or αEβ7 integrins. Inhibition of the α4β7 integrin is a shared mechanism with natalizumab, however vedolizumab binds solely to the α4β7 but not the α4β1 integrin, unlike natalizumab which binds to both. As a result, natalizumab modulates the systemic immune system and is associated with other side effects such as progressive multifocal leukoencephalopathy (PML).
Metabolism

The expected consequence of metabolism is proteolytic degradation to small peptides and individual amino acids, and receptor-mediated clearance.

Route of eliminationRenal clearance is negligible as vedolizumab is a high molecular weight protein.
Half lifeVedolizumab has a long terminal elimination half life of 336 to 362 hr.
Clearance

Vedolizumab has a low clearance of 0.180 to 0.266 ml/hr/kg.

ToxicityLong-term studies in animals have not been performed to evaluate the carcinogenic potential, mutagenicity, or possible impairments to fertility. Elevated transaminase levels with or without elevated bilirubin has occurred in patients who have received this drug. Progressive multifocal leukoencephalopathy (PML) has not been reported with use of this drug, however it has occurred in patients who have received different integrin receptor antagonists and is therefore considered a risk for this product. Use of vedolizumab may increase risk of developing infections, and one study found that nasopharyngitis occurs more frequently with vedolizumab than with placebo for CD patients (Wang et al, 2014).
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous300 mg/5mL
Powder for solutionintravenous300 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2012151248 No2012-05-022032-05-02Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
isoelectric point7.6European Medicines Agency Assessment Report (Procedure No.: EMEA/H/C/002782/0000)
References
Synthesis ReferenceNot Available
General References
  1. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [PubMed:19509315 ]
  2. Krupka N, Baumgart DC: Designing biologic selectivity for inflammatory bowel disease--role of vedolizumab. Drug Des Devel Ther. 2014 Dec 17;9:147-54. doi: 10.2147/DDDT.S50348. eCollection 2015. [PubMed:25552903 ]
  3. Wang MC, Zhang LY, Han W, Shao Y, Chen M, Ni R, Wang GN, Wei FX, Zhang YW, Xu XD, Zhang YC: PRISMA--efficacy and safety of vedolizumab for inflammatory bowel diseases: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2014 Dec;93(28):e326. doi: 10.1097/MD.0000000000000326. [PubMed:25526490 ]
External Links
ATC CodesL04AA33
AHFS Codes
  • 56:92
PDB EntriesNot Available
FDA labelDownload (281 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Vedolizumab.
BelimumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Belimumab.
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Vedolizumab.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Vedolizumab.
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Vedolizumab.
golimumabThe risk or severity of adverse effects can be increased when golimumab is combined with Vedolizumab.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Vedolizumab.
LeflunomideThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Leflunomide.
LenalidomideThe risk or severity of adverse effects can be increased when Lenalidomide is combined with Vedolizumab.
NatalizumabThe risk or severity of adverse effects can be increased when Vedolizumab is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Vedolizumab.
PomalidomideThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Vedolizumab.
RoflumilastRoflumilast may increase the immunosuppressive activities of Vedolizumab.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Vedolizumab.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vedolizumab.
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Vedolizumab.
TofacitinibVedolizumab may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Vedolizumab.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antibody
General Function:
Metal ion binding
Specific Function:
Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On act...
Gene Name:
ITGA4
Uniprot ID:
P13612
Molecular Weight:
114898.745 Da
References
  1. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [PubMed:19509315 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antibody
General Function:
Virus receptor activity
Specific Function:
Integrin alpha-4/beta-7 (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin alpha-4/beta-7 interacts with the cell surface adhesion molecules MADCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract. Interacts also with VCAM1 and fibronectin, ...
Gene Name:
ITGB7
Uniprot ID:
P26010
Molecular Weight:
86902.415 Da
References
  1. Soler D, Chapman T, Yang LL, Wyant T, Egan R, Fedyk ER: The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009 Sep;330(3):864-75. doi: 10.1124/jpet.109.153973. Epub 2009 Jun 9. [PubMed:19509315 ]
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Drug created on February 20, 2015 15:30 / Updated on August 17, 2016 12:24