Etanercept

Title: Etanercept
CAS Registry Number: 185243-69-0
CAS Name: 1-235-Tumor necrosis factor receptor (human) fusion protein with 236-467-immunoglobulin G1 (human g1-chain Fc fragment)
Additional Names: human tumor necrosis factor receptor p75 Fc fusion protein; TNFR:Fc
Trademarks: Enbrel (Wyeth)
Literature References: Recombinant protein consisting of the human soluble TNF receptor p75 linked to the Fc portion of human immunoglobulin G1. Dimerizes via the cysteine residues in the Fc fragment to form an immunoglobulin-like structure. Inhibits the biological effects of tumor necrosis factor, q.v. Description of prepn and medicinal use: C. A. Smith, C. A. Jacobs, WO 9406476; eidem, US 5605690 (1994, 1997 both to Immunex). Clinical pharmacokinetics: H. Lee et al., Clin. Pharmacol. Ther. 73, 348 (2003). Clinical trial as monotherapy in plaque psoriasis: C. L. Leonardi et al., N. Engl. J. Med. 349, 2014 (2003). Review of clinical experience in rheumatoid and psoriatic arthritis: B. Goffe, J. C. Cather, J. Am. Acad. Dermatol. 49, S105-S111 (2003); S. Nanda, J. M. Bathon, Expert Opin. Pharmacother. 5, 1175-1186 (2004).
Therap-Cat: Anti-inflammatory; antipsoriatic.
Keywords: Antipsoriatic; Anti-inflammatory (Biological Response Modifier).
Etanidazole Etaqualone eta-Tocopherol Eterobarb Etersalate

Etanercept
Enbrel.jpg
Clinical data
Trade names Enbrel
AHFS/Drugs.com monograph
Pregnancy cat. B2 (Au), B (U.S.)
Legal status S4 (Au), POM (UK), ℞-only (U.S.)
Routes Subcutaneous
Pharmacokinetic data
Bioavailability 58–76% (SC)
Metabolism Reticuloendothelial system (speculative)
Half-life 70–132 hours
Identifiers
CAS number 185243-69-0
ATC code L04AB01
PubChem SID10099
DrugBank DB00005
UNII OP401G7OJC YesY
KEGG D00742
ChEMBL CHEMBL1201572
Chemical data
Formula C2224H3475N621O698S36 
Mol. mass 51234.9 g/mol

Etanercept (trade name Enbrel) is a biopharmaceutical that treats autoimmune diseases by interfering with tumor necrosis factor (TNF; a soluble inflammatory cytokine) by acting as a TNF inhibitor. It has U.S. F.D.A. approval to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. TNF-alpha is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.[1]

Etanercept is a fusion protein produced by recombinant DNA. It fuses the TNF receptor to the constant end of the IgG1 antibody. First, the developers isolated the DNA sequence that codes the human gene for soluble TNF receptor 2, which is a receptor that binds to tumor necrosis factor-alpha. Second, they isolated the DNA sequence that codes the human gene for the Fc end of immunoglobulin G1 (IgG1). Third, they linked the DNA for TNF receptor 2 to the DNA for IgG1 Fc. Finally, they expressed the linked DNA to produce a protein that links the protein for TNF receptor 2 to the protein for IgG1 Fc.

The prototypic fusion protein was first synthesized and shown to be highly active and unusually stable as a modality for blockade of TNF in vivo in the early 1990s by Bruce A. Beutler, an academic researcher then at the University of Texas Southwestern Medical Center at Dallas, and his colleagues.[2][3][4] These investigators also patented the protein,[5] selling all rights to its use to Immunex, a biotechnology company that was acquired by Amgen in 2002.[6]

It is a large molecule, with a molecular weight of 150 kDa., that binds to TNFα and decreases its role in disorders involving excess inflammation in humans and other animals, including autoimmune diseases such as ankylosing spondylitis,[7] juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and, potentially, in a variety of other disorders mediated by excess TNFα.

In North America, etanercept is co-marketed by Amgen and Pfizer under the trade name Enbrel in two separate formulations, one in powder form, the other as a pre-mixed liquid. Wyeth was the sole marketer of Enbrel outside North America excluding Japan where Takeda Pharmaceuticals markets the drug.

Etanercept is an example of a protein-based drug created using the tools of biotechnology and conceived through an understanding afforded by modern cell biology.