DB05332 - Romiplostim
| Identification | |
|---|---|
| Name | Romiplostim |
| Accession Number | DB05332 |
| Type | biotech |
| Description | Romiplostim is a thrombopoiesis stimulating dimer Fc-peptide fusion protein (peptibody) to increase platelet production through activation of the thrombopoietin receptor. The peptibody molecule has two identical single-chain subunits, each one is made up of 269 amino acid residues. Each subunit consists of an IgG1 Fc carrier domain that is covalently attached to a polypeptide sequence that contains two binding domains to interact with thrombopoietin receptor c-Mpl. Each domain consists of 14 amino acids. Interestingly, romiplostim's amino acid sequence is not similar to that of endogenous thrombopoietin. Romiplostim is produced by recombinant DNA technology in Escherichia coli. FDA approved on August 22, 2008. |
| Structure |
|
| Categories (*) | |
| Molecular Weight | 59 kDa |
| Groups | approved |
| Monoisotopic Weight | Not Available |
| Pharmacology | |
| Indication | Treatment of chronic immune thrombocytopenic purpura. |
| Mechanism of action | Romiplostim is a thrombopoietin receptor agonist that activates intracellular transcriptional pathways via c-Mpl to increase production of platelets. It also works similarly to thrombopoietin (TPO), an endogenous glycoprotein hormone that regulates the production of platelets in the bone marrow. |
| Absorption | Cmax, healthy volunteers, subQ = 24-36 hours; Cmax, immune thrombocytopenia patients, subQ = 7-50 hours (median = 14 hours). Not affected by age, weight, or gender. Accumulation does not occur after six weekly doses of 3 mcg/kg romiplostim. |
| Protein binding | Not Available |
| Biotransformation | Not Available |
| Route of elimination | Renal clearance (more dominant mode of clearance as dose increases) and binding to c-Mpl receptors (dominant mode of clearance at low doses) |
| Toxicity | The most common adverse reactions (>= 5% higher patient incidence in Nplate versus placebo) are arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, and paresthesia. Headache was the most commonly reported adverse reaction that did not occur at >= 5% higher patient incidence in Nplate versus placebo. LD50 = 980 mg/kg. |
| Affected organisms |
|
| Interactions | |
| Drug Interactions | Not Available |
| Food Interactions | Not Available |
Targets
| Thrombopoietin receptor | |
|---|---|
| Name | Thrombopoietin receptor |
| Gene Name | MPL |
| Pharmacological action | yes |
| Actions | agonist |
| References |
|
| DTHybrid score | 1.1667 |
Predictions
| Id | Partner name | Gene Name | Score |
|---|---|---|---|
| 6176 | UDP-glucuronosyltransferase 1-3 | UGT1A3 | 0.075 |
| 6022 | UDP-glucuronosyltransferase 1-1 | UGT1A1 | 0.0679 |
| 1490 | Solute carrier organic anion transporter family member 1B1 | SLCO1B1 | 0.0616 |
| 4924 | Cytochrome P450 2C8 | CYP2C8 | 0.0485 |
| 4200 | Cytochrome P450 1A2 | CYP1A2 | 0.0454 |