Erlotinib - Revision history

Alexander Berchansky at 14:39, 17 November 2019

Alexander Berchansky — Sun, 17 Nov 2019 14:39:16 GMT

←Older revision		Revision as of 14:39, 17 November 2019
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	* Importance: It is one of the best selling and most effective treatments for several types of cancer. It is an improved version of [[Iressa]].		* Importance: It is one of the best selling and most effective treatments for several types of cancer. It is an improved version of [[Iressa]].
	* See [[Pharmaceutical Drugs]] for more information about other drugs and disorders		* See [[Pharmaceutical Drugs]] for more information about other drugs and disorders
-		+	* See also [[Journal:JBSD:26\|Investigation on the Site-Selective Binding of Bovine Serum Albumin by Erlotinib Hydrochloride]]
	===Mechanism of Action===		===Mechanism of Action===
	[[EGFR\|Epidermal Growth Factor Receptors]] are overexpressed in many types of human [[Cancer\|carcinomas]] including lung, pancreatic, and breast cancer, and are often mutated. This overexpression leads to excessive activation of the anti-apoptotic [[Ras]] signalling cascade, resulting in uncontrolled [[DNA_Replication\|DNA synthesis]] and cell proliferation. Studies have revealed that the <scene name='Erlotinib/Kinase/1'>EGFR tyrosine kinase domain</scene> is responsible for activating this Ras signaling cascade. Upon binding ligands like Epidermal Growth Factor, EGFR dimerizes and autophosphorylates several tyrosine residues at its C-terminal domain. Upon phosphorylation, EGFR undergoes a conformational change, revealing an additional binding site capable of eliciting downstream activation of other signaling proteins.<ref>PMID:6090945</ref><ref>PMID:16729045</ref> Erlotinib inhibits the EGFR tyrosine kinase by <scene name='Erlotinib/Bound/1'>binding to the ATP-binding site</scene> located within the kinase domain. EGFR uses residues Asp 831, Lys 721, Thr 766, Leu 820, Gly 772, Phe 771, Leu 694, Pro 770, Met 769, Leu 768, Gln 767 & Ala 719 to tightly bind the inhibitor. Unable to bind ATP, EGFR is incapable of autophosphorylating its C-terminal tyrosines, and the uncontrolled cell-proliferation signal is terminated.<ref>PMID:15284455</ref><ref>PMID:11129168</ref>		[[EGFR\|Epidermal Growth Factor Receptors]] are overexpressed in many types of human [[Cancer\|carcinomas]] including lung, pancreatic, and breast cancer, and are often mutated. This overexpression leads to excessive activation of the anti-apoptotic [[Ras]] signalling cascade, resulting in uncontrolled [[DNA_Replication\|DNA synthesis]] and cell proliferation. Studies have revealed that the <scene name='Erlotinib/Kinase/1'>EGFR tyrosine kinase domain</scene> is responsible for activating this Ras signaling cascade. Upon binding ligands like Epidermal Growth Factor, EGFR dimerizes and autophosphorylates several tyrosine residues at its C-terminal domain. Upon phosphorylation, EGFR undergoes a conformational change, revealing an additional binding site capable of eliciting downstream activation of other signaling proteins.<ref>PMID:6090945</ref><ref>PMID:16729045</ref> Erlotinib inhibits the EGFR tyrosine kinase by <scene name='Erlotinib/Bound/1'>binding to the ATP-binding site</scene> located within the kinase domain. EGFR uses residues Asp 831, Lys 721, Thr 766, Leu 820, Gly 772, Phe 771, Leu 694, Pro 770, Met 769, Leu 768, Gln 767 & Ala 719 to tightly bind the inhibitor. Unable to bind ATP, EGFR is incapable of autophosphorylating its C-terminal tyrosines, and the uncontrolled cell-proliferation signal is terminated.<ref>PMID:15284455</ref><ref>PMID:11129168</ref>

Joel L. Sussman at 17:12, 16 January 2017

Joel L. Sussman — Mon, 16 Jan 2017 17:12:49 GMT

←Older revision		Revision as of 17:12, 16 January 2017
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-	<StructureSection load='' size='~~350~~' side='right' scene='Erlotinib/Erlotinib/1' caption='Erlotinib, also known as Tarceva'>	+	<StructureSection load='' size='450' side='right' scene='Erlotinib/Erlotinib/1' caption='Erlotinib, also known as Tarceva'>
	__TOC__		__TOC__
	===Better Known as: Tarceva===		===Better Known as: Tarceva===

Joel L. Sussman at 12:19, 15 January 2017

Joel L. Sussman — Sun, 15 Jan 2017 12:19:26 GMT

←Older revision		Revision as of 12:19, 15 January 2017
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-	<~~applet~~ load="" size="350~~" color~~=~~"" frame~~=~~"true" spin="on" Scene ="~~Erlotinib/Erlotinib/1~~" align="right"~~ caption="Erlotinib, also known as Tarceva"/>	+	<StructureSection load='' size='350' side='right' scene='Erlotinib/Erlotinib/1' caption='Erlotinib, also known as Tarceva'>
		+	__TOC__
	===Better Known as: Tarceva===		===Better Known as: Tarceva===
	* Marketed By: Genentech, OSI Pharmaceutials, & Roche		* Marketed By: Genentech, OSI Pharmaceutials, & Roche
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	</tr>		</tr>
	</table>		</table>
-		+	</StructureSection>
	===References===		===References===
	<references/>		<references/>
	__NOEDITSECTION__		__NOEDITSECTION__
-	__NOTOC__

Michal Harel at 11:48, 29 February 2016

Michal Harel — Mon, 29 Feb 2016 11:48:24 GMT

←Older revision		Revision as of 11:48, 29 February 2016
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-	<applet load="" size="~~450~~" color="" frame="true" spin="on" Scene ="Erlotinib/Erlotinib/1" align="right" caption="Erlotinib, also known as Tarceva"/>	+	<applet load="" size="350" color="" frame="true" spin="on" Scene ="Erlotinib/Erlotinib/1" align="right" caption="Erlotinib, also known as Tarceva"/>
	===Better Known as: Tarceva===		===Better Known as: Tarceva===
	* Marketed By: Genentech, OSI Pharmaceutials, & Roche		* Marketed By: Genentech, OSI Pharmaceutials, & Roche
-	* Major Indication: Pancreatic & Small ~~Cel~~ Lung [[Cancer]]	+	* Major Indication: Pancreatic & Small Cell Lung [[Cancer]]
	* Drug Class: [[EGFR]] Inhibitor		* Drug Class: [[EGFR]] Inhibitor
	* Date of FDA Approval (Expiration): 2005 (2020)		* Date of FDA Approval (Expiration): 2005 (2020)

David Canner at 09:13, 11 December 2010

David Canner — Sat, 11 Dec 2010 09:13:29 GMT

←Older revision		Revision as of 09:13, 11 December 2010
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-	<applet load="" size="~~480~~" color="" frame="true" spin="on" Scene ="Erlotinib/Erlotinib/1" align="right" caption="Erlotinib, also known as Tarceva"/>	+	<applet load="" size="450" color="" frame="true" spin="on" Scene ="Erlotinib/Erlotinib/1" align="right" caption="Erlotinib, also known as Tarceva"/>
	===Better Known as: Tarceva===		===Better Known as: Tarceva===
	* Marketed By: Genentech, OSI Pharmaceutials, & Roche		* Marketed By: Genentech, OSI Pharmaceutials, & Roche

David Canner at 16:33, 9 December 2010

David Canner — Thu, 09 Dec 2010 16:33:59 GMT

←Older revision		Revision as of 16:33, 9 December 2010
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	===Pharmacokinetics===		===Pharmacokinetics===
-	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="55%">	+	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="50%">
	<tr>		<tr>
	<td style="width:auto; vertical-align:top;border-width:0px; border-style:inset">		<td style="width:auto; vertical-align:top;border-width:0px; border-style:inset">

David Canner at 16:32, 9 December 2010

David Canner — Thu, 09 Dec 2010 16:32:53 GMT

←Older revision		Revision as of 16:32, 9 December 2010
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	===Pharmacokinetics===		===Pharmacokinetics===
-	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="50%">	+	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="55%">
	<tr>		<tr>
	<td style="width:auto; vertical-align:top;border-width:0px; border-style:inset">		<td style="width:auto; vertical-align:top;border-width:0px; border-style:inset">

David Canner at 13:32, 9 December 2010

David Canner — Thu, 09 Dec 2010 13:32:50 GMT

←Older revision		Revision as of 13:32, 9 December 2010
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	<tr>		<tr>
	<td style="width:auto; vertical-align:top;border-width:0px; border-style:inset">		<td style="width:auto; vertical-align:top;border-width:0px; border-style:inset">
-	<div style="~~overflow:auto;~~ height:100%; width: 100%">	+	<div style="height:100%; width: 100%">
	{{:Tyrosine Kinase Inhibitor Pharmacokinetics}}		{{:Tyrosine Kinase Inhibitor Pharmacokinetics}}
	</div>		</div>

David Canner at 13:29, 9 December 2010

David Canner — Thu, 09 Dec 2010 13:29:38 GMT

←Older revision		Revision as of 13:29, 9 December 2010
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	===Pharmacokinetics===		===Pharmacokinetics===
-	~~{\| class~~="~~wikitable~~" ~~border~~="1" width="55%" style="~~text~~-align:~~center~~"	+	<table style="background: cellspacing="0px" align="" cellpadding="0px" width="50%">
-	\|-	+	<tr>
-	~~! colspan~~="~~4" align="center"\| EGFR Inhibitor [[Pharmacokinetics]] Comparison at Equivalent Dosages <ref>PMID~~:~~16609030</ref><ref>PMID~~:~~17482782</ref><ref>D. Smith et al. Br J Clin Pharmacol. 2009 April~~; ~~67(4)~~: ~~421–426.</ref~~>	+	<td style="width:auto; vertical-align:top;border-width:0px; border-style:inset">
-	\|-	+	<div style="overflow:auto; height:100%; width: 100%">
-	~~! Parameter~~	+	{{:Tyrosine Kinase Inhibitor Pharmacokinetics}}
-	~~! [[Erlotinib]]~~ <br/>~~(Tarceva)~~	+	</div>
-	~~! [[Gefitinib]]~~ <br/>~~(Iressa)~~	+	</td>
-	~~! [[Lapatinib]]~~ <br/>~~(Tykerb)~~	+	</tr>
-	\|-	+	</table>
-	~~! [[Pharmacokinetics#Tmax\|T<sub>max~~</~~sub~~>~~]] (hr)~~	+
-	~~! 2.0~~	+
-	~~! 5.4~~	+
-	~~! 4~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Cmax\|C<sub>max</sub>]] (ng/ml)~~	+
-	~~! 69.6~~	+
-	~~! 130~~	+
-	~~! 115~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Bioavailability_.28F.29\|Bioavailability]] (%)~~	+
-	~~! 99~~	+
-	~~! 59~~	+
-	~~! Variable~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Protein_Binding\|Protein Binding]] (%)~~	+
-	~~! 93~~	+
-	~~! 90~~	+
-	~~! 99~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Half_Life_.28T1.2F2.29\|T<sub>1/2</sub>]] (hr)~~	+
-	~~! 9.4~~	+
-	~~! 26.9~~	+
-	~~! 9.6~~	+
-	\|-	+
-	~~! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)~~	+
-	~~! 20577~~	+
-	~~! 3850~~	+
-	~~! 1429~~	+
-	\|-	+
-	~~! Typical Dosage (mg)~~	+
-	~~! 150~~	+
-	~~! 250~~	+
-	~~! 100~~	+
-	\|-	+
-	~~! Metabolism~~	+
-	~~! Hepatic - (CYP3A4)~~	+
-	~~! Hepatic - (CYP3A4)~~	+
-	~~! Hepatic - (CYP3A4)~~	+
-	\|}	+

	===References===		===References===

David Canner at 15:36, 8 December 2010

David Canner — Wed, 08 Dec 2010 15:36:47 GMT

←Older revision		Revision as of 15:36, 8 December 2010
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	* 2009 Sales: $1.2 Billion		* 2009 Sales: $1.2 Billion
	* Importance: It is one of the best selling and most effective treatments for several types of cancer. It is an improved version of [[Iressa]].		* Importance: It is one of the best selling and most effective treatments for several types of cancer. It is an improved version of [[Iressa]].
-	* ~~The following is a list of Pharmacokinetic Parameters.~~ See: [[Pharmaceutical Drugs]] for more information	+	* See [[Pharmaceutical Drugs]] for more information about other drugs and disorders

	===Mechanism of Action===		===Mechanism of Action===
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	{\| class="wikitable" border="1" width="55%" style="text-align:center"		{\| class="wikitable" border="1" width="55%" style="text-align:center"
	\|-		\|-
-	! colspan="4" align="center"\| EGFR Inhibitor [[~~Pharmaceutical_Drugs#Pharmacokinetics_Translated\|~~Pharmacokinetics]] Comparison at Equivalent Dosages <ref>PMID:16609030</ref><ref>PMID:17482782</ref><ref>D. Smith et al. Br J Clin Pharmacol. 2009 April; 67(4): 421–426.</ref>	+	! colspan="4" align="center"\| EGFR Inhibitor [[Pharmacokinetics]] Comparison at Equivalent Dosages <ref>PMID:16609030</ref><ref>PMID:17482782</ref><ref>D. Smith et al. Br J Clin Pharmacol. 2009 April; 67(4): 421–426.</ref>
	\|-		\|-
	! Parameter		! Parameter
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	! [[Lapatinib]] <br/>(Tykerb)		! [[Lapatinib]] <br/>(Tykerb)
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Tmax\|T<sub>max</sub>]] (hr)	+	! [[Pharmacokinetics#Tmax\|T<sub>max</sub>]] (hr)
	! 2.0		! 2.0
	! 5.4		! 5.4
	! 4		! 4
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Cmax\|C<sub>max</sub>]] (ng/ml)	+	! [[Pharmacokinetics#Cmax\|C<sub>max</sub>]] (ng/ml)
	! 69.6		! 69.6
	! 130		! 130
	! 115		! 115
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Bioavailability_.28F.29\|Bioavailability]] (%)	+	! [[Pharmacokinetics#Bioavailability_.28F.29\|Bioavailability]] (%)
	! 99		! 99
	! 59		! 59
	! Variable		! Variable
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Protein_Binding\|Protein Binding]] (%)	+	! [[Pharmacokinetics#Protein_Binding\|Protein Binding]] (%)
	! 93		! 93
	! 90		! 90
	! 99		! 99
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Half_Life_.28T1.2F2.29\|T<sub>1/2</sub>]] (hr)	+	! [[Pharmacokinetics#Half_Life_.28T1.2F2.29\|T<sub>1/2</sub>]] (hr)
	! 9.4		! 9.4
	! 26.9		! 26.9
	! 9.6		! 9.6
	\|-		\|-
-	! [[~~Pharmaceutical_Drugs~~#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)	+	! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29\|AUC]] (ng/ml/hr)
	! 20577		! 20577
	! 3850		! 3850