Sandbox 9888 - Revision history

Bryan Nguyen. at 15:54, 5 December 2016

Bryan Nguyen. — Mon, 05 Dec 2016 15:54:20 GMT

←Older revision		Revision as of 15:54, 5 December 2016
Line 22:		Line 22:
	In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref name="wong"/>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor of TNF-R. If an adequate amount of Remicade, or other competitive inhibitor, is introduced the TNF-α binding interface will be obstructed, thus preventing TNF-α from participating further in diseases.		In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref name="wong"/>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor of TNF-R. If an adequate amount of Remicade, or other competitive inhibitor, is introduced the TNF-α binding interface will be obstructed, thus preventing TNF-α from participating further in diseases.

-	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref name="liang"/>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref name="liang"/>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.	+	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/2'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref name="liang"/>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref name="liang"/>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.

	== Diseases ==		== Diseases ==

Bryan Nguyen. at 15:42, 5 December 2016

Bryan Nguyen. — Mon, 05 Dec 2016 15:42:56 GMT

←Older revision		Revision as of 15:42, 5 December 2016
Line 6:		Line 6:
	Remicade (Infliximab) is a chimeric IgG1 monoclonal antibody consisting of 597 amino acids, weighing 149,000 Daltons <ref name="liang">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 via genetic engineering<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 name="liang"/>. <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 name="liang"/>. 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 name="liang">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 via genetic engineering<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 name="liang"/>. <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 name="liang"/>. 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 a cell are neutralized when bound to high affinity receptor binding sites on the drug<ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref name="liang"/><ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. 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 a cell are neutralized when bound to high affinity receptor binding sites on the drug<ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref name="liang"/><ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/6'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.

	== History of Remicade ==		== History of Remicade ==

Zach Schuhmacher. at 16:16, 27 November 2016

Zach Schuhmacher. — Sun, 27 Nov 2016 16:16:35 GMT

←Older revision		Revision as of 16:16, 27 November 2016
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	== Structure ==		== Structure ==

-	Remicade (Infliximab) is a chimeric IgG1 monoclonal antibody consisting of 597 amino acids, weighing 149,000 Daltons <ref name="liang">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 name="liang"/>. <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 name="liang"/>. 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 name="liang">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 via genetic engineering<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 name="liang"/>. <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 name="liang"/>. 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 a cell are neutralized when bound to ~~the drugs~~ high affinity receptor binding sites <ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref name="liang"/><ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. 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 a cell are neutralized when bound to high affinity receptor binding sites on the drug<ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref name="liang"/><ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.

	== History of Remicade ==		== History of Remicade ==

-	Originally in search of an immunotherapy drug to combat cancer, Dr. Jan Vilcek and a team of researches made the remarkable discovery of a promising protein, tumor necrosis factor alpha <ref name="businessIn"/>. TNF-α,is a cytokine secreted by macrophages to elicit ~~inflammation~~. Vilcek initially discovered the protein while studying the growth of tumors in transplantable animals, such as murine mice <ref name="businessIn"/>. It was found that this protein could not only block the growth of such tumors, but could even rid the mice completely of cancerous cells <ref name="businessIn"/>. This left many hopeful that TNF could also be employed as a therapeutic agent to fight cancers in humans.	+	Originally in search of an immunotherapy drug to combat cancer, Dr. Jan Vilcek and a team of researches made the remarkable discovery of a promising protein, tumor necrosis factor alpha <ref name="businessIn"/>. TNF-α is a cytokine secreted by macrophages to elicit an inflammatory resopnse. Vilcek initially discovered the protein while studying the growth of tumors in transplantable animals, such as murine mice <ref name="businessIn"/>. It was found that this protein could not only block the growth of such tumors, but could even rid the mice completely of cancerous cells <ref name="businessIn"/>. This left many hopeful that TNF could also be employed as a therapeutic agent to fight cancers in humans.

	Beginning human trials, Vilcek and his team caught the attention of several drug companies, especially Centocor <ref name="businessIn"/>. Their hope was to have discovered a means of treating cancer using the body’s own immune system. Rather, the extraordinary protein they had discovered in 1993 was highly toxic, even at low doses <ref name="businessIn"/>. Although, the study did not result in the desired outcome, the team further researched the use of TNF for other clinical applications.		Beginning human trials, Vilcek and his team caught the attention of several drug companies, especially Centocor <ref name="businessIn"/>. Their hope was to have discovered a means of treating cancer using the body’s own immune system. Rather, the extraordinary protein they had discovered in 1993 was highly toxic, even at low doses <ref name="businessIn"/>. Although, the study did not result in the desired outcome, the team further researched the use of TNF for other clinical applications.
Line 20:		Line 20:
	Upon the injection of Remicade into the body, the drug is dispersed throughout the bloodstream and to the tissues. Depending on the patient’s body surface index, the dosage of the drug administered will vary.		Upon the injection of Remicade into the body, the drug is dispersed throughout the bloodstream and to the tissues. Depending on the patient’s body surface index, the dosage of the drug administered will vary.

-	In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref name="wong"/>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor to TNF-R. If an adequate amount is introduced, the interface will be obstructed, thus preventing TNF-α from participating further in diseases.	+	In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref name="wong"/>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor of TNF-R. If an adequate amount of Remicade, or other competitive inhibitor, is introduced the TNF-α binding interface will be obstructed, thus preventing TNF-α from participating further in diseases.

	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref name="liang"/>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref name="liang"/>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.		Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref name="liang"/>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref name="liang"/>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.

Bryan Nguyen. at 14:33, 17 November 2016

Bryan Nguyen. — Thu, 17 Nov 2016 14:33:36 GMT

←Older revision		Revision as of 14:33, 17 November 2016
Line 6:		Line 6:
	Remicade (Infliximab) is a chimeric IgG1 monoclonal antibody consisting of 597 amino acids, weighing 149,000 Daltons <ref name="liang">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 name="liang"/>. <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 name="liang"/>. 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 name="liang">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 name="liang"/>. <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 name="liang"/>. 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 ~~(TNF-R?)~~ on ~~TNF-α~~ are neutralized when bound to the drugs high affinity receptor binding sites <ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref name="liang"/><ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. 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 a cell are neutralized when bound to the drugs high affinity receptor binding sites <ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref name="liang"/><ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.

	== History of Remicade ==		== History of Remicade ==
Line 22:		Line 22:
	In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref name="wong"/>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor to TNF-R. If an adequate amount is introduced, the interface will be obstructed, thus preventing TNF-α from participating further in diseases.		In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref name="wong"/>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor to TNF-R. If an adequate amount is introduced, the interface will be obstructed, thus preventing TNF-α from participating further in diseases.

-	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref name="liang"/>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. ~~(ASK ABOUT ACIDIC CHAIN SUBSTITUTIONS)~~ The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref name="liang"/>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.	+	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref name="liang"/>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref name="liang"/>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.

	== Diseases ==		== Diseases ==

Bryan Nguyen. at 19:44, 8 November 2016

Bryan Nguyen. — Tue, 08 Nov 2016 19:44:10 GMT

←Older revision		Revision as of 19:44, 8 November 2016
Line 6:		Line 6:
	Remicade (Infliximab) is a chimeric IgG1 monoclonal antibody consisting of 597 amino acids, weighing 149,000 Daltons <ref name="liang">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 name="liang"/>. <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 name="liang"/>. 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 name="liang">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 name="liang"/>. <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 name="liang"/>. 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 (TNF-R?) on TNF-α are neutralized when bound to the drugs high affinity receptor binding sites <ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.	+	After intravenously injecting Infliximab, the p55 and p75 receptors (TNF-R?) on TNF-α are neutralized when bound to the drugs high affinity receptor binding sites <ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref name="liang"/><ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.

	== History of Remicade ==		== History of Remicade ==

Bryan Nguyen. at 19:41, 8 November 2016

Bryan Nguyen. — Tue, 08 Nov 2016 19:41:56 GMT

←Older revision		Revision as of 19:41, 8 November 2016
Line 6:		Line 6:
	Remicade (Infliximab) is a chimeric IgG1 monoclonal antibody consisting of 597 amino acids, weighing 149,000 Daltons <ref name="liang">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 name="liang"/>. <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 name="liang"/>. 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 name="liang">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 name="liang"/>. <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 name="liang"/>. 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 (TNF-R?) on TNF-α are neutralized when bound to the drugs high affinity receptor binding sites <ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/1'>hydrophobic interface</scene> <ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.	+	After intravenously injecting Infliximab, the p55 and p75 receptors (TNF-R?) on TNF-α are neutralized when bound to the drugs high affinity receptor binding sites <ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/2'>hydrophobic interface</scene> <ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.

	== History of Remicade ==		== History of Remicade ==

Bryan Nguyen. at 18:57, 8 November 2016

Bryan Nguyen. — Tue, 08 Nov 2016 18:57:31 GMT

←Older revision		Revision as of 18:57, 8 November 2016
Line 6:		Line 6:
	Remicade (Infliximab) is a chimeric IgG1 monoclonal antibody consisting of 597 amino acids, weighing 149,000 Daltons <ref name="liang">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 name="liang"/>. <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 name="liang"/>. 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 name="liang">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 name="liang"/>. <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 name="liang"/>. 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 (TNF-R?) 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 <scene name='74/744162/Hydrophobic_interface/1'>hydrophobic interface</scene> <ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>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~~>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.	+	After intravenously injecting Infliximab, the p55 and p75 receptors (TNF-R?) on TNF-α are neutralized when bound to the drugs high affinity receptor binding sites <ref name="wong">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 name="liang"/>. Specifically, TNF-α contributes to the stability by creating a <scene name='74/744162/Hydrophobic_interface/1'>hydrophobic interface</scene> <ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>Tyr-141 side chain</scene> <ref name="liang"/>. 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 name="liang"/>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.

	== History of Remicade ==		== History of Remicade ==
Line 20:		Line 20:
	Upon the injection of Remicade into the body, the drug is dispersed throughout the bloodstream and to the tissues. Depending on the patient’s body surface index, the dosage of the drug administered will vary.		Upon the injection of Remicade into the body, the drug is dispersed throughout the bloodstream and to the tissues. Depending on the patient’s body surface index, the dosage of the drug administered will vary.

-	In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref~~>PMID:17916444<~~/~~ref~~>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor to TNF-R. If an adequate amount is introduced, the interface will be obstructed, thus preventing TNF-α from participating further in diseases.	+	In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref name="wong"/>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor to TNF-R. If an adequate amount is introduced, the interface will be obstructed, thus preventing TNF-α from participating further in diseases.

-	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref~~>PMID:23504311<~~/~~ref~~>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. (ASK ABOUT ACIDIC CHAIN SUBSTITUTIONS) The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref~~>PMID:23504311<~~/~~ref~~>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.	+	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref name="liang"/>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. (ASK ABOUT ACIDIC CHAIN SUBSTITUTIONS) The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref name="liang"/>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.

	== Diseases ==		== Diseases ==
Line 37:		Line 37:

	<b>Ankylosing Spondylitis:</b>		<b>Ankylosing Spondylitis:</b>
-	Ankylosing Spondylitis is an inflammatory disease affecting the spine and large joints in the body <ref>Grainger, R., & Harrison, A. A. (2007). Infliximab in the treatment of ankylosing spondylitis. Biologics, 1(2), 163-171.</ref>. Symptoms typically begin to appear in early adulthood causing reduced flexibility, eventually leading to a hunched-forward posture. With Remicade, signs and symptoms can be lessened in patients who are experiencing active Ankylosing Spondylitis by inhibiting TNF-α <ref~~> Grainger, R., & Harrison, A. A. (2007). Infliximab in the treatment of ankylosing spondylitis. Biologics, 1(2), 163-171.<~~/~~ref~~>.	+	Ankylosing Spondylitis is an inflammatory disease affecting the spine and large joints in the body <ref name="grainger">Grainger, R., & Harrison, A. A. (2007). Infliximab in the treatment of ankylosing spondylitis. Biologics, 1(2), 163-171.</ref>. Symptoms typically begin to appear in early adulthood causing reduced flexibility, eventually leading to a hunched-forward posture. With Remicade, signs and symptoms can be lessened in patients who are experiencing active Ankylosing Spondylitis by inhibiting TNF-α <ref name="grainger"/>.

	<b>Plaque Psoriasis:</b>		<b>Plaque Psoriasis:</b>
-	Plaque psoriasis is the most common form of the disease, appearing as raised, red patches covered with a off-white buildup of dead skin cells <ref>PMID:19537380</ref>. These plaques typically appear on the scalp, knees, elbows and lower back <ref~~>PMID:19537380<~~/~~ref~~>. Remicade has been FDA approved for the treatment of adult patients expressing severe, chronic symptoms <ref~~>PMID:19537380<~~/~~ref~~>. The severity of the disease is ultimately assessed by a physician to determine if Remicade is the right course of action in consideration with other possible therapies <ref~~>PMID:19537380<~~/~~ref~~>.	+	Plaque psoriasis is the most common form of the disease, appearing as raised, red patches covered with a off-white buildup of dead skin cells <ref name="kircik">PMID:19537380</ref>. These plaques typically appear on the scalp, knees, elbows and lower back <ref name="kircik"/>. Remicade has been FDA approved for the treatment of adult patients expressing severe, chronic symptoms <ref name="kircik"/>. The severity of the disease is ultimately assessed by a physician to determine if Remicade is the right course of action in consideration with other possible therapies <ref name="kircik"/>.

	<b>Psoriatic Arthritis:</b>		<b>Psoriatic Arthritis:</b>

Bryan Nguyen. at 18:25, 8 November 2016

Bryan Nguyen. — Tue, 08 Nov 2016 18:25:43 GMT

←Older revision		Revision as of 18:25, 8 November 2016
Line 4:		Line 4:
	== Structure ==		== Structure ==

-	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 name="liang">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 name="liang"/>. <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 name="liang"/>. 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 (TNF-R?) 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 <scene name='74/744162/Hydrophobic_interface/1'>hydrophobic interface</scene> <ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>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>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.		After intravenously injecting Infliximab, the p55 and p75 receptors (TNF-R?) 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 <scene name='74/744162/Hydrophobic_interface/1'>hydrophobic interface</scene> <ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>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>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.

Bryan Nguyen. at 14:32, 8 November 2016

Bryan Nguyen. — Tue, 08 Nov 2016 14:32:27 GMT

←Older revision		Revision as of 14:32, 8 November 2016
Line 4:		Line 4:
	== Structure ==		== Structure ==

-	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 (TNF-R?) 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 <scene name='74/744162/Hydrophobic_interface/1'>hydrophobic interface</scene><ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>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>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.	+	After intravenously injecting Infliximab, the p55 and p75 receptors (TNF-R?) 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 <scene name='74/744162/Hydrophobic_interface/1'>hydrophobic interface</scene> <ref>PMID:2777790</ref> through amino acid residues such as the <scene name='74/744162/Tyr_141_atom/3'>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>. To view the loop residues of the full structure complex, <scene name='74/744162/Loops_tnf_3molecule/1'>click here</scene>. These favorable interactions are essential to the complex formed between TNF-α and infliximab Fab.

	== History of Remicade ==		== History of Remicade ==
Line 20:		Line 20:
	Upon the injection of Remicade into the body, the drug is dispersed throughout the bloodstream and to the tissues. Depending on the patient’s body surface index, the dosage of the drug administered will vary.		Upon the injection of Remicade into the body, the drug is dispersed throughout the bloodstream and to the tissues. Depending on the patient’s body surface index, the dosage of the drug administered will vary.

-	In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR)<ref>PMID:17916444</ref>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines<ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor to TNF-R. If an adequate amount is introduced, the interface will be obstructed, thus preventing TNF-α from participating further in diseases.	+	In determining the proper amount of how much of the drug should be injected, Remicade is able to sufficiently block TNF-α from interacting with the TNF receptors (TNFR) <ref>PMID:17916444</ref>. Thus, inhibiting the receptor from signaling production of IL-1 and IL-6, both of which are pro-inflammatory cytokines <ref>PMID:27100432</ref>. When this occurs, Remicade acts as a competitive inhibitor to TNF-R. If an adequate amount is introduced, the interface will be obstructed, thus preventing TNF-α from participating further in diseases.

-	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops<ref>PMID:23504311</ref>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. (ASK ABOUT ACIDIC CHAIN SUBSTITUTIONS) The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer<ref>PMID:23504311</ref>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.	+	Once the complex forms, it is stabilized by the amino acid residues <scene name='74/744162/Cdef_residues/1'>Gln67–His73 and Gln102–Lys112</scene> of the C-D and E-F loops <ref>PMID:23504311</ref>. Particularly, the weak interactions between the loops and side chains, allows for a stronger binding affinity. (ASK ABOUT ACIDIC CHAIN SUBSTITUTIONS) The strongest interaction between the two proteins is best seen in the peak region of TNF. This arises when TNF-α is in its active form and exists as a trimer <ref>PMID:23504311</ref>. Although, research has offered some insight into the mechanisms of how Remicade effectively inhibits TNF-α, studies have not shown a clear understanding of the extensive underlying network. Thus, more research into this matter should be pursued.

	== Diseases ==		== Diseases ==
Line 40:		Line 40:

	<b>Plaque Psoriasis:</b>		<b>Plaque Psoriasis:</b>
-	Plaque psoriasis is the most common form of the disease, appearing as raised, red patches covered with a off-white buildup of dead skin cells<ref>PMID:19537380</ref>. These plaques typically appear on the scalp, knees, elbows and lower back<ref>PMID:19537380</ref>. Remicade has been FDA approved for the treatment of adult patients expressing severe, chronic symptoms<ref>PMID:19537380</ref>. The severity of the disease is ultimately assessed by a physician to determine if Remicade is the right course of action in consideration with other possible therapies<ref>PMID:19537380</ref>.	+	Plaque psoriasis is the most common form of the disease, appearing as raised, red patches covered with a off-white buildup of dead skin cells <ref>PMID:19537380</ref>. These plaques typically appear on the scalp, knees, elbows and lower back <ref>PMID:19537380</ref>. Remicade has been FDA approved for the treatment of adult patients expressing severe, chronic symptoms <ref>PMID:19537380</ref>. The severity of the disease is ultimately assessed by a physician to determine if Remicade is the right course of action in consideration with other possible therapies <ref>PMID:19537380</ref>.

	<b>Psoriatic Arthritis:</b>		<b>Psoriatic Arthritis:</b>

Bryan Nguyen. at 21:53, 7 November 2016

Bryan Nguyen. — Mon, 07 Nov 2016 21:53:39 GMT

←Older revision		Revision as of 21:53, 7 November 2016
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	<b>Ulcerative Colitis:</b>		<b>Ulcerative Colitis:</b>
-	Similar to Crohn’s disease, Ulcerative Colitis is a chronic inflammatory bowel disease that causes inflammation in the digestive tract, particularly the sigmoid colon of the large intestine and rectum <ref name="FDA"></~~ref~~>. Levels of TNF-α in stool samples is a technique used to assess the level of the disease in patients <ref name="FDA"></~~ref~~>. To promote intestinal healing, Remicade is a drug that can be prescribed to prevent the use of steroids in adults with moderate to severe symptoms <ref name="FDA"></~~ref~~>.	+	Similar to Crohn’s disease, Ulcerative Colitis is a chronic inflammatory bowel disease that causes inflammation in the digestive tract, particularly the sigmoid colon of the large intestine and rectum <ref name="FDA"/>. Levels of TNF-α in stool samples is a technique used to assess the level of the disease in patients <ref name="FDA"/>. To promote intestinal healing, Remicade is a drug that can be prescribed to prevent the use of steroids in adults with moderate to severe symptoms <ref name="FDA"/>.

	<b>Ankylosing Spondylitis:</b>		<b>Ankylosing Spondylitis:</b>