DT-Web

DB00038 - Oprelvekin


Identification
Name Oprelvekin
Accession Number DB00038 (BIOD00021, BTD00021)
Type biotech
Description Oprelvekin, the active ingredient in Neumega(R) 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(R) is stimulation of megakaryocytopoiesis and thrombopoiesis. In mice and nonhuman primate studies Neumega(R) has shown potent thrombopoietic activity in compromised hematopoiesis, including moderately to severely myelosuppressed animals. In these studies, Neumega(R) 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 19047.2000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Increases reduced platelet levels due to chemotherapy
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.
Absorption Absolute bioavailability is over 80%.
Protein binding Not Available
Biotransformation 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.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Dihydrocodeine May increase the serum levels of opioid analgesics. It is recommended to monitor therapy for the signs and symptoms of respiratory depression and enhanced sedation.
Food Interactions Not Available

Targets


Interleukin-11 receptor alpha chain
Name Interleukin-11 receptor alpha chain
Gene Name IL11RA
Pharmacological action yes
Actions agonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 2

Predictions


Id Partner name Gene Name Score
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