| Primary information |
|---|
| ThPP ID | Th1202 |
| Therapeutic Peptide/Protein Name | Pembrolizumab |
| Sequence | NA view full sequnce in fasta |
| Functional Classification | IIIc |
| Molecular Weight | 146286.2902 |
| Chemical Formula | C6504H10004N1716O2036S46 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting Point (℃) | NA |
| Half Life | 28 days. |
| 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. |
| Indication/Disease | 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. 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. |
| Pharmacodynamics | In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. |
| Mechanism of Action | 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 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. |
| Toxicity | Since 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. |
| Metabolism | |
| Absorption | |
| Volume of Distribution | |
| Clearance | 0.22 L/day |
| Categories | Antineoplastic and Immunomodulating Agents |
| Patents Number | US2012135408 |
| Date of Issue | 40997 |
| Date of Expiry | 48302 |
| Drug Interaction | NA |
| Target | Programmed cell death protein 1 |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Keytruda |
| Company | Merck Sharp & Dohme Corp. |
| Brand Discription | Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. |
| Prescribed for | KEYTRUDA® (pembrolizumab) is indicated for the treatment of patients with unresectable or metastatic melanoma. |
| Chemical Name | NA |
| Formulation | 100 mg of pembrolizumab in 4 mL of solution. |
| Physcial Appearnce | lyophilized powder |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. |
| Contraindication | NA |
| Side Effects | Immune-mediated pneumonitis; Immune-mediated colitis; Immune-mediated hepatitis; Immune-mediated endocrinopathies; Immune-mediated nephritis and renal dysfunction; Other immune-mediated adverse reactions; Infusion-related reactions. |
| Useful Link | http://www.rxlist.com/keytruda-drug/side-effects-interactions.htm |
| PubMed ID | 27803020, 28315636, 28303768, 28293123, 28292987, 28291584, 28288994, 28285592, 28285535 |
| 3-D Structure | Th1202 Heavy chianor (Download)Th1202 Light chian (View) or (Download) |