Sandbox 9888

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m
Line 6: Line 6:
Remicade (Infliximab) is a chimeric IgG1 monoclonal antibody consisting of 597 amino acids, weighing 149,000 Daltons <ref> PMID: 23504311 </ref>. This chimeric monoclonal antibody is produced when the variable regions of a murine antibody (25%) is fused with the constant regions of a human antibody (75%) at the hinge region through a genetic engineering process <ref> PMID: 17592358 </ref>. Within the hinge region, intramolecular disulfide bonds stabilize the two fragment antigen binding regions (Fab) to the fragment crystallizable region (Fc). <scene name='74/744162/Variable_chains_hc/1'>Click here to view separated Fab and Fc regions</scene>. The Fab regions are comprised of both a heavy and light chain, while the Fc region consist of only a heavy chain. Located in the folded Vh and Ch domains of the heavy chain, amino acid residues Glu-1 to Thr-226 are found <ref> PMID: 23504311 </ref>. <scene name='74/744162/Heavy_chain/1'>The heavy chain region is highlighted here, and only (1 of 3) molecules are shown, for simplicity</scene>. In addition, the <scene name='74/744162/Light_chain/1'>light chain</scene> is composed of residues Asp-1 to Cys-214 that fold into the Vl and Cl domain <ref> PMID: 23504311 </ref>. The heavy and light chain at the N-terminus form the variable region that functions as a receptor binding site.
Remicade (Infliximab) is a chimeric IgG1 monoclonal antibody consisting of 597 amino acids, weighing 149,000 Daltons <ref> PMID: 23504311 </ref>. This chimeric monoclonal antibody is produced when the variable regions of a murine antibody (25%) is fused with the constant regions of a human antibody (75%) at the hinge region through a genetic engineering process <ref> PMID: 17592358 </ref>. Within the hinge region, intramolecular disulfide bonds stabilize the two fragment antigen binding regions (Fab) to the fragment crystallizable region (Fc). <scene name='74/744162/Variable_chains_hc/1'>Click here to view separated Fab and Fc regions</scene>. The Fab regions are comprised of both a heavy and light chain, while the Fc region consist of only a heavy chain. Located in the folded Vh and Ch domains of the heavy chain, amino acid residues Glu-1 to Thr-226 are found <ref> PMID: 23504311 </ref>. <scene name='74/744162/Heavy_chain/1'>The heavy chain region is highlighted here, and only (1 of 3) molecules are shown, for simplicity</scene>. In addition, the <scene name='74/744162/Light_chain/1'>light chain</scene> is composed of residues Asp-1 to Cys-214 that fold into the Vl and Cl domain <ref> PMID: 23504311 </ref>. The heavy and light chain at the N-terminus form the variable region that functions as a receptor binding site.
-
After intravenously injecting Infliximab, the p55 and p75 receptors on TNF-α are neutralized when bound to the drugs high affinity receptor binding sites <ref> PMID: 17916444 </ref>. The complex formed is stabilized through the vast array of weak interactions between the two proteins, such as hydrogen bonds, salt bridges, and Van der Waal forces <ref> PMID: 23504311 </ref>. Specifically, TNF-α contributes to the stability by creating a hydrophobic interface through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/1'>Tyr-141 side chain</scene> <ref> PMID: 23504311 </ref>. This interface is formed primarily by the C-D and E-F <scene name='74/744162/Loops_tnf/1'>loop residues</scene> connecting the antiparallel 8-stranded Beta sheets <ref> PMID: 23504311 </ref>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.
+
After intravenously injecting Infliximab, the p55 and p75 receptors on TNF-α are neutralized when bound to the drugs high affinity receptor binding sites <ref> PMID: 17916444 </ref>. The complex formed is stabilized through the vast array of weak interactions between the two proteins, such as hydrogen bonds, salt bridges, and Van der Waal forces <ref> PMID: 23504311 </ref>. Specifically, TNF-α contributes to the stability by creating a hydrophobic interface through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/1'>Tyr-141 side chain</scene> <ref> PMID: 23504311 </ref>. This interface is formed primarily by the C-D and E-F <scene name='74/744162/Loops_tnf/2'>loop residues</scene> connecting the antiparallel 8-stranded Beta sheets <ref> PMID: 23504311 </ref>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.
== History of Remicade ==
== History of Remicade ==

Revision as of 13:46, 3 November 2016

Remicade (Infliximab)

Caption for this structure

Drag the structure with the mouse to rotate

References

  1. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab. J Biol Chem. 2013 May 10;288(19):13799-807. doi: 10.1074/jbc.M112.433961. Epub, 2013 Mar 15. PMID:23504311 doi:10.1074/jbc.M112.433961
  2. de Ridder L, Benninga MA, Taminiau JA, Hommes DW, van Deventer SJ. Infliximab use in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007 Jul;45(1):3-14. PMID:17592358 doi:http://dx.doi.org/10.1097/MPG.0b013e31803e171c
  3. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab. J Biol Chem. 2013 May 10;288(19):13799-807. doi: 10.1074/jbc.M112.433961. Epub, 2013 Mar 15. PMID:23504311 doi:10.1074/jbc.M112.433961
  4. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab. J Biol Chem. 2013 May 10;288(19):13799-807. doi: 10.1074/jbc.M112.433961. Epub, 2013 Mar 15. PMID:23504311 doi:10.1074/jbc.M112.433961
  5. Wong M, Ziring D, Korin Y, Desai S, Kim S, Lin J, Gjertson D, Braun J, Reed E, Singh RR. TNFalpha blockade in human diseases: mechanisms and future directions. Clin Immunol. 2008 Feb;126(2):121-36. Epub 2007 Oct 3. PMID:17916444 doi:http://dx.doi.org/10.1016/j.clim.2007.08.013
  6. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab. J Biol Chem. 2013 May 10;288(19):13799-807. doi: 10.1074/jbc.M112.433961. Epub, 2013 Mar 15. PMID:23504311 doi:10.1074/jbc.M112.433961
  7. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab. J Biol Chem. 2013 May 10;288(19):13799-807. doi: 10.1074/jbc.M112.433961. Epub, 2013 Mar 15. PMID:23504311 doi:10.1074/jbc.M112.433961
  8. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab. J Biol Chem. 2013 May 10;288(19):13799-807. doi: 10.1074/jbc.M112.433961. Epub, 2013 Mar 15. PMID:23504311 doi:10.1074/jbc.M112.433961
  9. 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 Ramsey, L. (2015). One of the world’s blockbuster drugs might not exist if its research hadn't flopped in a major way. Retrieved from http://www.businessinsider.com/remicade-would-have-failed-as-a-cancer-drug-2015-12
  10. Wong M, Ziring D, Korin Y, Desai S, Kim S, Lin J, Gjertson D, Braun J, Reed E, Singh RR. TNFalpha blockade in human diseases: mechanisms and future directions. Clin Immunol. 2008 Feb;126(2):121-36. Epub 2007 Oct 3. PMID:17916444 doi:http://dx.doi.org/10.1016/j.clim.2007.08.013
  11. Steenholdt C, Coskun M, Buhl S, Bendtzen K, Ainsworth MA, Brynskov J, Nielsen OH. Circulating Cytokines and Cytokine Receptors in Infliximab Treatment Failure Due to TNF-alpha Independent Crohn Disease. Medicine (Baltimore). 2016 Apr;95(16):e3417. doi: 10.1097/MD.0000000000003417. PMID:27100432 doi:http://dx.doi.org/10.1097/MD.0000000000003417
  12. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab. J Biol Chem. 2013 May 10;288(19):13799-807. doi: 10.1074/jbc.M112.433961. Epub, 2013 Mar 15. PMID:23504311 doi:10.1074/jbc.M112.433961
  13. Liang S, Dai J, Hou S, Su L, Zhang D, Guo H, Hu S, Wang H, Rao Z, Guo Y, Lou Z. Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab. J Biol Chem. 2013 May 10;288(19):13799-807. doi: 10.1074/jbc.M112.433961. Epub, 2013 Mar 15. PMID:23504311 doi:10.1074/jbc.M112.433961
  14. 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 14.8 REMICADE (Infliximab) for IV injection. (2002). ( No. 1242). Malvern, PA: Centocor, INC.
  15. Grainger, R., & Harrison, A. A. (2007). Infliximab in the treatment of ankylosing spondylitis. Biologics, 1(2), 163-171.
  16. Grainger, R., & Harrison, A. A. (2007). Infliximab in the treatment of ankylosing spondylitis. Biologics, 1(2), 163-171.
  17. Kircik LH, Del Rosso JQ. Anti-TNF agents for the treatment of psoriasis. J Drugs Dermatol. 2009 Jun;8(6):546-59. PMID:19537380
  18. Kircik LH, Del Rosso JQ. Anti-TNF agents for the treatment of psoriasis. J Drugs Dermatol. 2009 Jun;8(6):546-59. PMID:19537380
  19. Kircik LH, Del Rosso JQ. Anti-TNF agents for the treatment of psoriasis. J Drugs Dermatol. 2009 Jun;8(6):546-59. PMID:19537380
  20. Kircik LH, Del Rosso JQ. Anti-TNF agents for the treatment of psoriasis. J Drugs Dermatol. 2009 Jun;8(6):546-59. PMID:19537380
  21. National Psoriasis Foundation. (2016). Moderate to severe psoriasis and psoriatic arthritis: Biologic drugs. Retrieved from https://www.psoriasis.org/about-psoriasis/treatments/biologics
Personal tools