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Identification
NameNivolumab
Accession NumberDB09035
TypeBiotech
GroupsApproved
Description

Nivolumab is a fully human IgG4 monoclonal antibody that acts as an immunomodulator by blocking ligand activation of programmed cell death 1 (PD-1) receptor on T cells. It is indicated for use in patients with unresectable (cannot be surgically removed) or metastatic melanoma who no longer respond to other drugs. Nivolumab is administered as an intravenous infusion over 60 minutes every 2 weeks.

Protein structureDb09035
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Protein chemical formulaC6362H9862N1712O1995S42
Protein average weight143597.3811 Da
Sequences
>Heavy Chain Sequence
QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYY
ADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLVTVSSASTKGPS
VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS
VVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKP
KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT
VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC
LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV
MHEALHNHYTQKSLSLSLGK
>Light Chain Sequence
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCQQSSNWPRTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
SynonymsNot Available
External Identifiers
  • BMS-936558
  • GTPL7335
  • MDX-1106
  • ONO-4538
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Opdivoinjection10 mg/mLintravenousE.R. Squibb & Sons, L.L.C.2014-12-22Not applicableUs
Opdivosolution10 mgintravenousBristol Myers Squibb Canada2015-10-23Not applicableCanada
Opdivosolution10 mgintravenousBristol Myers Squibb Canada2015-10-23Not applicableCanada
Opdivoinjection10 mg/mLintravenousE.R. Squibb & Sons, L.L.C.2014-12-22Not applicableUs
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
UNII31YO63LBSN
CAS number946414-94-4
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
IndicationNivolumab is indicated for the treatment of unresectable or metastatic melanoma for patients who no longer respond to treatment with other drugs. It is intended for use in patients who have been previously treated with ipilimumab and is used for melanoma patients after treatment with ipilimumab and a BRAF inhibitor in patients whose tumors express BRAF V600 gene mutations. Historically there have been very few effective treatments for advanced melanoma, which is why this product was approved under an FDA accelerated program to allow earlier patient access.
PharmacodynamicsNot Available
Mechanism of actionNivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the programmed cell death 1 (PD-1) receptor and selectively blocks interaction with its programmed death ligands PD-L1 and PD-L2. Upregulation of PD-1 ligands occurs in some tumors and signalling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumour tissue. The inhibitory effect of PD-1 and its ligands occurs through the promotion of apoptosis in antigen specific T cells while simultaneously blocking apoptosis in suppressor T cells. Blocking PD-1 activity has been shown to lead to decreased tumour growth in mouse tumour models.
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AbsorptionThe intended route of administration is intravenous, therefore bioavailability is expected to be 100%.
Volume of distribution

8.0 L

Protein bindingNot Available
Metabolism

As nivolumab is an antibody, 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 life26.7 days
Clearance

9.5 mL/hr

ToxicityBased on data from animal studies, there is risk of fetal harm when administered to pregnant women. It is therefore advisable for pregnant women to use contraception during treatment and for 5 months afterwards. There have been reported cases of severe pneumonitis or interstitial lung disease, including fatal cases, with the use of nivolumab during clinical trials. Therefore, patients taking this drug should be monitored for signs and symptoms of pneumonitis. During clinical trials there have also been reports of the development of immune-mediated colitis, immune-mediated hepatitis with increased liver test abnormalities, immune-mediated nephritis and renal dysfunction, immune-mediated hypothyroidism and hyperthyroidism, and rare cases of other immune-mediated reactions such as pancreatitis, uveitis, demyelination, autoimmune neuropathy, adrenal insufficiency, and facial and abducens nerve paresis.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injectionintravenous10 mg/mL
Solutionintravenous10 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2013173223 No2013-05-132033-05-13Us
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. Taneja SS: Re: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. J Urol. 2012 Dec;188(6):2149. [PubMed:23289116 ]
  2. Tsai KK, Zarzoso I, Daud AI: PD-1 and PD-L1 antibodies for melanoma. Hum Vaccin Immunother. 2014;10(11):3111-6. doi: 10.4161/21645515.2014.983409. [PubMed:25625924 ]
  3. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS: Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3. [PubMed:24590637 ]
External Links
ATC CodesL01XC17
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (315 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
BelimumabThe risk or severity of adverse effects can be increased when Nivolumab is combined with Belimumab.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antibody
General Function:
Signal transducer activity
Specific Function:
Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. Possible cell death inducer, in association with other factors.
Gene Name:
PDCD1
Uniprot ID:
Q15116
Molecular Weight:
31646.635 Da
References
  1. Taneja SS: Re: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. J Urol. 2012 Dec;188(6):2149. [PubMed:23289116 ]
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Drug created on February 24, 2015 16:02 / Updated on March 14, 2016 10:05