Identification

Summary

Oprelvekin is a form of recombinant interleukin-11 used to stimulate production of megakaryocytes and platelets in patients with or at risk of thrombocytopenia after chemotherapy.

Generic Name
Oprelvekin
DrugBank Accession Number
DB00038
Background

Oprelvekin, the active ingredient in Neumega®, is recombinant Interleukin-11 (IL-11), which is produced in Escherichia coli (E. coli) by recombinant DNA technology. With a molecular mass of approximately 19,000 daltons, the non-glycosylated protein is 177 amino acids in length in comparison to the natural IL-11, which is 178 amino acid long. However, it displays comparable biological activity compared to the natural IL-11 in vitro and in vivo. Oprelvekin works by stimulating megakaryocytopoiesis and thrombopoiesis. In mice and nonhuman primate studies of animals with moderate and severe myelosuppression, in addition to compromised hematopoiesis, oprelvekin was shown to potently induce thrombopoiesis and improve platelet nadirs and accelerated platelet recoveries compared to controls. In animal studies, oprelvekin was also shown to regulate intestinal epithelium growth by enhancing healing of gastrointestinal lesions, inhibit adiopegenesis and macrophageal released pro-inflammatory cytokines, and induce acute phase protein synthesis.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interleukin-based products
Protein Structure
Db00038
Protein Chemical Formula
C854H1411N253O235S2
Protein Average Weight
19047.2 Da
Sequences
>DB00038 sequence
GPPPGPPRVSPDPRAELDSTVLLTRSLLADTRQLAAQLRDKFPADGDHNLDSLPTLAMSA
GALGALQLPGVLTRLRADLLSYLRHVQWLRRAGGSSLKTLEPELGTLQARLDRLLRRLQL
LMSRLALPQPPPDPPAPPLAPPSSAWGGIRAAHAILGGLHLTLDWAVRGLLLLKTRL
Download FASTA Format
Synonyms
  • IL-11
  • Interleukin 11
  • Interleukin-11
  • Oprelvekin
  • Recombinant interleukin-11
External IDs
  • YM 294

Pharmacology

Indication

Indicated for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia.[Label]

Pharmacology
Reduce drug development failure rates
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Oprelvekin promotes hematopoiesis by stimulating megakaryocytopoiesis and thrombopoiesis. It is used in adult patients with nonmyeloid malignancies to prevent severe thrombocytopenia and reduce the need for platelet transfusions following therapies that cause myelosuppression. Its use is prioritized in patients who are at an elevated risk for developing severe thrombocytopenia. In clinical trials, oprelvekin has shown potent thrombopoietic activity in individuals with compromised hematopoiesis.

Mechanism of action

Oprelvekin binds to the interleukin 11 receptor which leads to a cascade of signal transduction events. Its pharmacological action mimics the biological activity of endogenous IL-11, which is a thrombopoietic growth factor that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production.

TargetActionsOrganism
AInterleukin-11 receptor subunit alpha
agonist
Humans
Absorption

Absolute bioavailability is over 80%.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

The kidney is the primary route of elimination. The amount of intact Neumega in urine was low, indicating that the molecule was metabolized before excretion.

Half-life

6.9 +/- 1.7 hrs

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NeumegaKit5 mg/1mLSubcutaneousWyeth Bio Pharma Division Of Wyeth Pharmaceuticals Inc., A Subsidiary Of Pfizer Inc.1997-11-012017-04-30US flag

Categories

ATC Codes
L03AC02 — Oprelvekin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
HM5641GA6F
CAS number
145941-26-0

References

General References
Not Available
UniProt
P20809
Genbank
M57765
PubChem Substance
46506470
RxNav
1311380
ChEMBL
CHEMBL1201573
Therapeutic Targets Database
DAP001287
PharmGKB
PA164747991
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Oprelvekin
FDA label
Download (57.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentPancytopenia Due to Chemotherapy1
3CompletedPreventionThrombocytopenia Chemotherapy Induced1
3RecruitingTreatmentNasopharyngeal Carcinoma (NPC)1
2CompletedPreventionVon Willebrand's Disease1
2CompletedTreatmentBreast Cancer / Gestational Trophoblastic Disease / Malignant Lymphomas / Neuroblastoma (NB) / Ovarian Cancer / Renal Cancers / Sarcomas / Testicular germ cell tumour1
2CompletedTreatmentCrohn's Disease (CD) / Inflammatory Bowel Diseases (IBD)1
2CompletedTreatmentHemophilia As / Von Willebrand's Disease1
2CompletedTreatmentLeukemia Chronic Myelogenous Leukemia (CML) / Leukemias1
2CompletedTreatmentVon Willebrand's Disease1
2TerminatedPreventionVon Willebrand's Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Physicians Total Care Inc.
  • Wyeth Pharmaceuticals
Dosage Forms
FormRouteStrength
KitSubcutaneous5 mg/1mL
Prices
Unit descriptionCostUnit
Neumega 5 mg vial352.9USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.070Not Available
isoelectric point11.16Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for interleukin-11. The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 can utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex may be involved in the co...
Gene Name
IL11RA
Uniprot ID
Q14626
Uniprot Name
Interleukin-11 receptor subunit alpha
Molecular Weight
45221.925 Da
References
  1. Nandurkar HH, Robb L, Begley CG: The role of IL-II in hematopoiesis as revealed by a targeted mutation of its receptor. Stem Cells. 1998;16 Suppl 2:53-65. [Article]
  2. Li R, Hartley L, Robb L: Cloning of rat interleukin 11 and interleukin 11 receptor alpha chain and analysis of their expression in rat uterus in the peri-implantation period. Reproduction. 2001 Oct;122(4):593-600. [Article]
  3. Nandurkar HH, Hilton DJ, Nathan P, Willson T, Nicola N, Begley CG: The human IL-11 receptor requires gp130 for signalling: demonstration by molecular cloning of the receptor. Oncogene. 1996 Feb 1;12(3):585-93. [Article]
  4. Romas E, Udagawa N, Zhou H, Tamura T, Saito M, Taga T, Hilton DJ, Suda T, Ng KW, Martin TJ: The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures. J Exp Med. 1996 Jun 1;183(6):2581-91. [Article]
  5. Nandurkar HH, Robb L, Tarlinton D, Barnett L, Kontgen F, Begley CG: Adult mice with targeted mutation of the interleukin-11 receptor (IL11Ra) display normal hematopoiesis. Blood. 1997 Sep 15;90(6):2148-59. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 03, 2021 00:33