DT-Web

DB01257 - Eculizumab


Identification
Name Eculizumab
Accession Number DB01257
Type biotech
Description Soliris is a formulation of eculizumab which is a recombinant humanized monoclonal IgG2/4;κ antibody produced by murine myeloma cell culture and purified by standard bioprocess technology. Eculizumab contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of approximately 148 kDa.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 148000.0000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
Mechanism of action A genetic mutation in PNH patients leads to the generation of populations of abnormal RBCs (known as PNH cells) that are deficient in terminal complement inhibitors (CD-59), rendering PNH RBCs sensitive to persistent terminal complement-mediated destruction. The destruction and loss of these PNH cells (intravascular hemolysis) results in low RBC counts (anemia) and also fatigue, difficulty in functioning, pain, dark urine, shortness of breath, and blood clots. Eculizumab, the active ingredient in Soliris, is a monoclonal antibody that binds to the complement protein C5 specifically and with high affinity, thereby inhibiting its cleavage to C5a and C5b and subsequent generation of the terminal complement complex C5b-9. Soliris inhibits terminal complement mediated intravascular hemolysis in PNH patients and therefore the destruction of PNH erythrocytes that lack complement protection with CD-59.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Complement C5
Name Complement C5
Gene Name C5
Pharmacological action yes
Actions antibody
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Singer AL, Locke JE, Stewart ZA, Lonze BE, Hamilton JP, Scudiere JR, Anders RA, Rother RP, Brodsky RA, Cameron AM: Successful liver transplantation for Budd-Chiari syndrome in a patient with paroxysmal nocturnal hemoglobinuria treated with the anti-complement antibody eculizumab. Liver Transpl. 2009 May;15(5):540-3. - Pubmed
  • Kelly R, Richards S, Hillmen P, Hill A: The pathophysiology of paroxysmal nocturnal hemoglobinuria and treatment with eculizumab. Ther Clin Risk Manag. 2009;5:911-21. Epub . - Pubmed
  • Dmytrijuk A, Robie-Suh K, Cohen MH, Rieves D, Weiss K, Pazdur R: FDA report: eculizumab (Soliris) for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Oncologist. 2008 Sep;13(9):993-1000. Epub 2008 Sep 10. - Pubmed
  • Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L: Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007 Nov;25(11):1256-64. - Pubmed
  • Luzzatto L, Risitano AM, Notaro R: Paroxysmal nocturnal hemoglobinuria and eculizumab. Haematologica. 2010 Apr;95(4):523-6. - Pubmed
  • Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P, Roth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L: The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233-43. - Pubmed
  • Hillmen P, Muus P, Duhrsen U, Risitano AM, Schubert J, Luzzatto L, Schrezenmeier H, Szer J, Brodsky RA, Hill A, Socie G, Bessler M, Rollins SA, Bell L, Rother RP, Young NS: Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123-8. Epub 2007 Aug 16. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.125

Predictions


Id Partner name Gene Name Score
5898 Complement C3 C3 0.1064
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.0678
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.0678
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.0678
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0678
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.0671
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.0664
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