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Identification
NamePembrolizumab
Accession NumberDB09037
TypeBiotech
GroupsApproved
Description

Pembrolizumab is an antibody drug that targets the cell surface receptor programmed cell death protein 1 (PD-1) found on T cells. By preventing the binding of its ligands (PD-L1 and PD-L2), pembrolizumab induces an antitumor immune response. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Its use is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following therapy with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Due to its success in clinical trials, pembrolizumab was approved early to allow quick patient access and was given breakthrough therapy and orphan drug designation. Pembrolizumab (as Keytruda) was approved by the U.S. Food and Drug Administration to treat advanced cases of the most common type of lung malignancy, non-small cell lung cancer (NSCLC) on Oct. 2, 2015.

Protein structureDb09037
Related Articles
Protein chemical formulaC6504H10004N1716O2036S46
Protein average weight146286.2902 Da
Sequences
>Heavy Chain Sequence
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWMGGINPSNGGTNF
NEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARRDYRFDMGFDYWGQGTTVTVSS
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG
NVFSCSVMHEALHNHYTQKSLSLSLGK
>Light Chain Sequence
EIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLIYLASYLES
GVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTFGGGTKVEIKRTVAAPSVF
IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS
STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
SynonymsNot Available
External Identifiers
  • lambrolizumab
  • MK 3475
  • MK-3475
  • MK3475
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Keytrudainjection, solution25 mg/mLintravenousMerck Sharp & Dohme Corp.2015-01-15Not applicableUs
Keytrudapowder for solution50 mgintravenousMerck Canada Inc2015-06-01Not applicableCanada
Keytrudainjection, powder, lyophilized, for solution50 mg/2mLintravenousMerck Sharp & Dohme Corp.2014-09-04Not 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
UNIIDPT0O3T46P
CAS number1374853-91-4
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
IndicationFor the treatment of patients with unresectable or metastatic melanoma and disease progression following therapy with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It is also for the treatment of patients with metastatic NSCLC (non-small cell lung cancer) whose tumors express PD-L1 (as determined by an approved test) and who have disease progression on or after platinum-containing chemotherapy.
PharmacodynamicsNot Available
Mechanism of actionPembrolizumab is an antibody drug that targets the cell surface receptor programmed cell death protein 1 (PD-1) found on T cells. By preventing the binding of its ligands (PD-L1 and PD-L2), pembrolizumab induces an antitumor immune response. Upregulation of PD-1 ligands is a mechanism for tumours to evade antitumor immune response; when PD-1 binds its ligand, the T cell receives an inhibitory signal leading to T cell anergy and blockade of anti tumour immune response. Instead of directly targeting tumor tissue to induce tumor cell death, pembrolizumab acts as a checkpoint inhibitor to stimulate immune responses to eliminate cancer cells.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeElimination half life is 28 days.
Clearance

0.22 L/day

ToxicitySince therapy with pembrolizumab induces tumour regression by stimulation of immune responses, side effects may be caused by activating potentially self-reactive T cells. This includes immune-mediated pneumonitis, colitis, hypophysitis, nephritis and renal failure, hyperthyroidism and hypothyroidism, and hepatitis. Other adverse events such as myasthenic syndrome, optic neuritis, uveitis, arthritis, pancreatitis, partial seizures, and rhabdomnyolysis were reported to occur in less than 1% of patients during clinical trials. Female patients are advised to use highly effective contraception during and for 4 months following treatment due to the risk of fetal harm.
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/2mL
Injection, solutionintravenous25 mg/mL
Powder for solutionintravenous50 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2012135408 No2012-03-292032-03-29Us
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC, Patnaik A, Dronca R, Zarour H, Joseph RW, Boasberg P, Chmielowski B, Mateus C, Postow MA, Gergich K, Elassaiss-Schaap J, Li XN, Iannone R, Ebbinghaus SW, Kang SP, Daud A: Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014 Sep 20;384(9948):1109-17. doi: 10.1016/S0140-6736(14)60958-2. Epub 2014 Jul 15. [PubMed:25034862 ]
  2. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A: Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133. Epub 2013 Jun 2. [PubMed:23724846 ]
  3. Poole RM: Pembrolizumab: first global approval. Drugs. 2014 Oct;74(16):1973-81. doi: 10.1007/s40265-014-0314-5. [PubMed:25331768 ]
External Links
ATC CodesL01XC18
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (589 KB)
MSDSDownload (134 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonistantibody
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. McDermott J, Jimeno A: Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. Drugs Today (Barc). 2015 Jan;51(1):7-20. doi: 10.1358/dot.2015.51.1.2250387. [PubMed:25685857 ]
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Drug created on March 30, 2015 16:49 / Updated on March 14, 2016 10:05