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Identification
NameBrentuximab vedotin
Accession NumberDB08870
TypeBiotech
GroupsApproved
Description

Brentuximag vedotin or Adcetris® is an antibody-drug conjugate that combines an anti-CD30 antibody and the drug monomethyl auristatin E (MMAE). It is an anti-neoplastic agent used in the treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Brentuximag vedotin was approved in 2011, and in January 2012, the drug label was revised to include a boxed warning of progressive multifocal leukoencephalopathy and death following JC virus infection.

Protein structureNo structure small
Related Articles
Protein chemical formulaC6476H9930N1690O2030S40
Protein average weight150500.0 Da (range 149200-151800)
SequencesNot Available
Synonyms
cAC10-vcMMAE
External Identifiers
  • SGN-35
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Adcetrisinjection, powder, lyophilized, for solution50 mg/10.5mLintravenousSeattle Genetics, Inc.2011-08-25Not applicableUs
Adcetrispowder for solution50 mgintravenousSeattle Genetics Inc2013-02-19Not 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
UNII7XL5ISS668
CAS number914088-09-8
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
IndicationUsed in the treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma.
PharmacodynamicsBrentuximag vedotin causes apoptosis of tumor cells by preventing cell cycle progression of the G2 to M phase through disruption of the cytosolic mictrotuble network.
Mechanism of actionBrentuximab vedotin is composed of 3 parts: a chimeric human-murine IgG1 that targets CD30, monomethyl auristatin E (MMAE),which is a microtubule disrupting agent, and a protease-susceptible linker that covalently links the antibody and MMAE. The IgG1 antibody enables brentuximab vedotin to target tumor cells expressing CD30 on their cell surface then brentuximab vedotin gets internalized into the cell. Once inside, the linker is cleaved releasing MMAE which binds disrupts the microtuble network.
Related Articles
AbsorptionBrentuximab vedotin is administered only as an intravenous infusion so absorption is 100%.
Volume of distribution

The steady state volume of distribution is 6-10 L.

Protein bindingMMAE has a plasma protein binding range of 68-82%, and highly-protein bound drugs are not likely to displace it.
Metabolism

Only a small fraction of MMAE is metabolized primarily via oxidation by CYP3A4 and CYP3A5.

Route of eliminationMMAE is eliminated by the feces (with 72% unchanged) and urine.
Half lifeThe terminal half-life is 4-6 days.
Clearance

MMAE is cleared by the liver but not quantitative studies have been performed.

ToxicityThe most severe toxic reaction seen in patients is progressive multifocal leukoencephalopathy. Other toxicities include bone marrow suppression, infusion reactions, peripheral neuropathy, Stevens-Johnson syndrome, and tumor lysis syndrome.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous50 mg/10.5mL
Powder for solutionintravenous50 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis Reference

Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, Rejniak SX, Gordon KA, DeBlanc R, Toki BE, Law CL, Doronina SO, Siegall CB, Senter PD, Wahl AF: cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65. Epub 2003 Apr 24

General References
  1. Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, Rejniak SX, Gordon KA, DeBlanc R, Toki BE, Law CL, Doronina SO, Siegall CB, Senter PD, Wahl AF: cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65. Epub 2003 Apr 24. [PubMed:12714494 ]
External Links
ATC CodesL01XC12
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (217 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Brentuximab vedotin can be increased when it is combined with Abiraterone.
AmiodaroneThe serum concentration of Brentuximab vedotin can be increased when it is combined with Amiodarone.
AtazanavirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Atazanavir.
AtorvastatinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Atorvastatin.
AzithromycinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Azithromycin.
BelimumabThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Belimumab.
BleomycinThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Bleomycin.
BoceprevirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Boceprevir.
CarbamazepineThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Carbamazepine.
CarvedilolThe serum concentration of Brentuximab vedotin can be increased when it is combined with Carvedilol.
CeritinibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Brentuximab vedotin can be increased when it is combined with Cobicistat.
CrizotinibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Crizotinib.
CyclosporineThe serum concentration of Brentuximab vedotin can be increased when it is combined with Cyclosporine.
DaclatasvirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Daclatasvir.
DarunavirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Darunavir.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Brentuximab vedotin.
DipyridamoleThe serum concentration of Brentuximab vedotin can be increased when it is combined with Dipyridamole.
DronedaroneThe serum concentration of Brentuximab vedotin can be increased when it is combined with Dronedarone.
EliglustatThe serum concentration of Brentuximab vedotin can be increased when it is combined with Eliglustat.
EnzalutamideThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Enzalutamide.
ErythromycinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Erythromycin.
FlibanserinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Flibanserin.
FosphenytoinThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Fosphenytoin.
IbrutinibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Ibrutinib.
IdelalisibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Brentuximab vedotin can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Brentuximab vedotin can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Brentuximab vedotin can be increased when it is combined with Ketoconazole.
LapatinibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Lapatinib.
LeflunomideThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Leflunomide.
LomitapideThe serum concentration of Brentuximab vedotin can be increased when it is combined with Lomitapide.
LumacaftorThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Lumacaftor.
MefloquineThe serum concentration of Brentuximab vedotin can be increased when it is combined with Mefloquine.
MirabegronThe serum concentration of Brentuximab vedotin can be increased when it is combined with Mirabegron.
MitotaneThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Mitotane.
NatalizumabThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Natalizumab.
NefazodoneThe serum concentration of Brentuximab vedotin can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Nelfinavir.
NicardipineThe serum concentration of Brentuximab vedotin can be increased when it is combined with Nicardipine.
NilotinibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Nilotinib.
PhenobarbitalThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Brentuximab vedotin.
PosaconazoleThe serum concentration of Brentuximab vedotin can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Primidone.
ProgesteroneThe serum concentration of Brentuximab vedotin can be increased when it is combined with Progesterone.
PropranololThe serum concentration of Brentuximab vedotin can be increased when it is combined with Propranolol.
QuinidineThe serum concentration of Brentuximab vedotin can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Brentuximab vedotin can be increased when it is combined with Quinine.
RanolazineThe serum concentration of Brentuximab vedotin can be increased when it is combined with Ranolazine.
ReserpineThe serum concentration of Brentuximab vedotin can be increased when it is combined with Reserpine.
RifabutinThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Ritonavir.
RoflumilastRoflumilast may increase the immunosuppressive activities of Brentuximab vedotin.
RolapitantThe serum concentration of Brentuximab vedotin can be increased when it is combined with Rolapitant.
SaquinavirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Saquinavir.
SimeprevirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Simeprevir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Brentuximab vedotin.
SunitinibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Sunitinib.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Brentuximab vedotin.
TamoxifenThe serum concentration of Brentuximab vedotin can be increased when it is combined with Tamoxifen.
TelaprevirThe serum concentration of Brentuximab vedotin can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Telithromycin.
TesmilifeneThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Tesmilifene.
TipranavirThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Tipranavir.
TofacitinibBrentuximab vedotin may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Brentuximab vedotin.
VandetanibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Vandetanib.
VemurafenibThe serum concentration of Brentuximab vedotin can be increased when it is combined with Vemurafenib.
VerapamilThe serum concentration of Brentuximab vedotin can be increased when it is combined with Verapamil.
VinblastineThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Vinblastine.
VoriconazoleThe serum concentration of Brentuximab vedotin can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
binder
General Function:
Tumor necrosis factor-activated receptor activity
Specific Function:
Receptor for TNFSF8/CD30L. May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-B.
Gene Name:
TNFRSF8
Uniprot ID:
P28908
Molecular Weight:
63746.47 Da
References
  1. Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, Rejniak SX, Gordon KA, DeBlanc R, Toki BE, Law CL, Doronina SO, Siegall CB, Senter PD, Wahl AF: cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65. Epub 2003 Apr 24. [PubMed:12714494 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrateinhibitor
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Comments
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Drug created on May 01, 2013 14:50 / Updated on August 17, 2016 12:24