==== Reference: Usmani SS, Bedi G, Samuel JS, Singh S, Kalra S, Kumar P, et al. (2017) THPdb: Database of FDA-approved peptide and protein therapeutics. PLoS ONE 12(7) e0181748.====

Detailed description page of THPdb

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1604 details
Primary information
ThPP IDTh1130
Therapeutic Peptide/Protein NameBrentuximab vedotin
SequenceHeavy chain:QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVK view full sequnce in fasta
Functional ClassificationIIb
Molecular Weight149200-151800
Chemical FormulaC6476H9930N1690O2030S40
Isoelectric PointN.A.
HydrophobicityN.A.
Melting Point (℃)N.A.
Half LifeTerminal half-life is 4-6 days
DescriptionBrentuximag 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-cancer drug used to treat Hodgkin lymphoma and systemic anaplastic large cell lymphoma. It was approved in 2011 but in January 2012, the drug label was revised to include a boxed warning of progressive multifocal leukoencephalopathy and death following JC virus infection.
Indication/DiseaseUsed 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.
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.
MetabolismOnly a small fraction of MMAE is metabolized primarily via oxidation by CYP3A4 and CYP3A5.
AbsorptionBrentuximab vedotin is administered only as an Intravenous infusion so absorption is 100%.
Volume of DistributionThe steady state volume of distribution is 6-10 L.
ClearanceMMAE is cleared by the liver but not quantitative studies have been performed.
CategoriesN.A.
Patents NumberN.A.
Date of IssueN.A.
Date of ExpiryN.A.
Drug InteractionN.A.
TargetTumor necrosis factor receptor superfamily member 8
Information of corresponding available drug in the market
Brand NameAdcetris
CompanySeattle Genetics
Brand DiscriptionADCETRIS (brentuximab vedotin) is a CD30-directed antibody-drug conjugate (ADC) consisting of three components: 1) the chimeric IgG1 antibody cAC10, specific for human CD30, 2) the microtubule disrupting agent MMAE, and 3) a protease-cleavable linker that covalently attaches MMAE to cAC10. Brentuximab vedotin has an approximate molecular weight of 153 kDa. Approximately 4 molecules of MMAE are attached to each antibody molecule. Brentuximab vedotin is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule components are produced by chemical synthesis.
Prescribed forHodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates.
Chemical NameN.A.
FormulationFollowing reconstitution with 10.5 mL Sterile Water for Injection, USP, a solution containing 5 mg/mL brentuximab vedotin is produced. The reconstituted product contains 70 mg/mL trehalose dihydrate, 5.6 mg/mL sodium citrate dihydrate, 0.21 mg/mL citric acid monohydrate, and 0.20 mg/mL polysorbate 80 and water for injection. The pH is approximately 6.6.
Physcial AppearnceADCETRIS (brentuximab vedotin) for Injection is supplied as a sterile, white to off-white, preservative-free lyophilized cake or powder in single-use vials.
Route of AdministrationIntravenous infusion
Recommended DosageNormal renal and hepatic function (1.8 mg/kg up to 180 mg), Mild (creatinine clearance > 50-80 mL/min) or moderate (creatinine clearance 30-50 mL/min) (1.8 mg/kg up to 180 mg), Severe (creatinine clearance less than 30 mL/min) (Avoid use), Mild (Child-Pugh A) (1.2 mg/kg up to 120 mg), Moderate (Child-Pugh B) or severe (Child-Pugh C) (Avoid use).
Contraindicationconcomitant bleomycin due to pulmonary toxicity
Side EffectsPeripheral neuropathy, Anaphylaxis and Infusion Reactions, Hematologic Toxicities, Serious Infections and Opportunistic Infections, Tumor Lysis Syndrome, Increased Toxicity in the Presence of Severe Renal Impairment, Increased Toxicity in the Presence of Moderate or Severe Hepatic Impairment, Hepatotoxicity, Progressive Multifocal Leukoencephalopathy, Serious Dermatologic Reactions, Embryo-Fetal Toxicity
Useful Linkhttp://www.rxlist.com/adcetris-drug.htm http://www.adcetris.com/ http://en.wikipedia.org/wiki/Brentuximab_vedotin
PubMed ID25642958, 25641881, 25573987
3-D StructureTh1130 Heavy chain or (Download), Th1130 Light chain (View) or (Download)