Oprelvekin

Identification

Name
Oprelvekin
Accession Number
DB00038  (BTD00021, BIOD00021)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Interleukin-based products
Description

Oprelvekin, the active ingredient in Neumega® is recombinant Interleukin eleven, which is produced in Escherichia coli (E. coli) by recombinant DNA technology. The protein has a molecular mass of approximately 19,000 daltons, and is non-glycosylated. The polypeptide is 177 amino acids in length (the natural IL-11 has 178). This alteration has not resulted in measurable differences in bioactivity either in vitro or in vivo.

The primary hematopoietic activity of Neumega® is stimulation of megakaryocytopoiesis and thrombopoiesis. In mice and nonhuman primate studies Neumega® has shown potent thrombopoietic activity in compromised hematopoiesis, including moderately to severely myelosuppressed animals. In these studies, Neumega® improved platelet nadirs and accelerated platelet recoveries compared to controls.

In animal studies Oprelvekin also has non-hematopoetic activities. This includes the regulation of intestinal epithelium growth (enhanced healing of gastrointestinal lesions), the inhibition of adipogenesis, the induction of acute phase protein synthesis (e.g., fibrinogen), and inhibition of macrophageal released pro-inflammatory cytokines.

Protein structure
Db00038
Protein chemical formula
C854H1411N253O235S2
Protein average weight
19047.2 Da
Sequences
>DB00038 sequence
GPPPGPPRVSPDPRAELDSTVLLTRSLLADTRQLAAQLRDKFPADGDHNLDSLPTLAMSA
GALGALQLPGVLTRLRADLLSYLRHVQWLRRAGGSSLKTLEPELGTLQARLDRLLRRLQL
LMSRLALPQPPPDPPAPPLAPPSSAWGGIRAAHAILGGLHLTLDWAVRGLLLLKTRL
Download FASTA Format
Synonyms
  • Adipogenesis inhibitory factor
  • AGIF
  • IL-11
  • Interleukin-11 precursor
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NeumegaKitWyeth Bio Pharma Division Of Wyeth Pharmaceuticals Inc., A Subsidiary Of Pfizer Inc.1997-11-012017-04-30Us
Categories
UNII
HM5641GA6F
CAS number
145941-26-0

Pharmacology

Indication

Increases reduced platelet levels due to chemotherapy

Structured Indications
Pharmacodynamics

Oprelvekin is 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. The primary hematopoietic activity of Oprelvekin is stimulation of megakaryocytopoiesis and thrombopoiesis. 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. IL-11 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
Human
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Oprelvekin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Oprelvekin.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Oprelvekin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Oprelvekin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Oprelvekin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Oprelvekin.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Oprelvekin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Oprelvekin.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Oprelvekin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Oprelvekin.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Oprelvekin.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Oprelvekin.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Oprelvekin.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Oprelvekin.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Oprelvekin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Oprelvekin.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Oprelvekin.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Oprelvekin.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Oprelvekin.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
UniProt
P20809
Genbank
M57765
ChEMBL
CHEMBL1201573
Therapeutic Targets Database
DAP001287
PharmGKB
PA164747991
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Oprelvekin
ATC Codes
L03AC02 — Oprelvekin
FDA label
Download (57.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2TerminatedTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Splenic Marginal Zone Lymphoma / Waldenstrom's Macroglobulinemia (WM)1
2CompletedPreventionVon Willebrand 's disease Type 11
2CompletedTreatmentChronic Myelogenous Leukemia (CML) / Chronic Myeloid Leukemia (CML) / Leukemias1
2CompletedTreatmentHemophilia A / Von Willebrand 's disease Type 11
2CompletedTreatmentVon Willebrand 's disease Type 11
2TerminatedPreventionVon Willebrand 's disease Type 11
2TerminatedTreatmentSevere Thrombocytopenia1
Not AvailableRecruitingNot AvailableHemostatic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Kit
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

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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. [PubMed:11012177]
  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. [PubMed:11570967]
  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. [PubMed:8637716]
  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. [PubMed:8676079]
  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. [PubMed:9310465]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23