A database of FDA approved therapeutic peptides and proteins
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1604 details |
| Primary information | |
|---|---|
| ThPP ID | Th1130 |
| Therapeutic Peptide/Protein Name | Brentuximab vedotin |
| Sequence | Heavy chain:QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVK view full sequnce in fasta |
| Functional Classification | IIb |
| Molecular Weight | 149200-151800 |
| Chemical Formula | C6476H9930N1690O2030S40 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | Terminal half-life is 4-6 days |
| 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-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/Disease | Used in the treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma. |
| Pharmacodynamics | Brentuximag 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 Action | Brentuximab 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. |
| Toxicity | The 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. |
| Metabolism | Only a small fraction of MMAE is metabolized primarily via oxidation by CYP3A4 and CYP3A5. |
| Absorption | Brentuximab 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. |
| Clearance | MMAE is cleared by the liver but not quantitative studies have been performed. |
| Categories | N.A. |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | Tumor necrosis factor receptor superfamily member 8 |
| Information of corresponding available drug in the market | |
| Brand Name | Adcetris |
| Company | Seattle Genetics |
| Brand Discription | ADCETRIS (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 for | Hodgkin 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 Name | N.A. |
| Formulation | Following 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 Appearnce | ADCETRIS (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 Administration | Intravenous infusion |
| Recommended Dosage | Normal 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). |
| Contraindication | concomitant bleomycin due to pulmonary toxicity |
| Side Effects | Peripheral 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 Link | http://www.rxlist.com/adcetris-drug.htm http://www.adcetris.com/ http://en.wikipedia.org/wiki/Brentuximab_vedotin |
| PubMed ID | 25642958, 25641881, 25573987 |
| 3-D Structure | Th1130 Heavy chain or (Download), Th1130 Light chain (View) or (Download) |