Bevacizumab: Difference between revisions

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David Canner, Joel L. Sussman, Michal Harel, Alexander Berchansky

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-<applet   load="" size="480" color="" frame="true"  spin="on" Scene ="Rivastigmine/Riv/1" align="right" caption="Rivastigmine, also known as Exelon"/>
+<StructureSection load='' size='350' side='right' scene='Bevacizumab/Ba/1' caption='Model Bevacizumab, also known as Avastin (PDB code [[1igt]])'>
-===Better Known as: Exelon===
+__TOC__
-* Marketed By: Novartis<br />
-* Major Indication: [[Alzheimer's Disease]]<br />
+===Better Known as: Avastin===
-* Drug Class: [[Acetylcholinesterase]] Inhibitor
+* Marketed By: Genentech & Roche<br />
-* Date of FDA Approval (Patent Expiration): 2007 (<br />
+* Major Indication: Colorectal [[Cancer]]<br />
-* 2006 Sales: $220 Million<ref>Irena Melnikova, Therapies for Alzheimer's disease, Nature Reviews Drug Discovery 6, 341-342 (May 2007)</ref>
+* Drug Class: [[Vascular Endothelial Growth Factor]] Inhibitor - [[Monoclonal Antibody]]
-* Importance: One of the the first treatments for the symptoms of [[Alzheimer's Disease]], although no definitive proof exists as to whether it alters the progression of the disease.
+* Date of FDA Approval (Patent Expiration): 2004 (2019)
-* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information
+* 2009 Sales: $4.8 Billion
+* Importance: It is one of the best selling [[cancer]] treatments in history. Despite being effective against colorectal cancer, post-approval studies after accelerated approval revealed that Avastin was ineffective in treating breast cancer. Many question the $90,000/year bill to take Avastin when it extends life on average only 10 months.
+* See [[Pharmaceutical Drugs]] for more information about other drugs and disorders
 ===Mechanism of Action===
+[[Vascular Endothelial Growth Factor]] (VEGF) is a signal protein often over-expressed in cancerous cells. It is responsible for activating [[Vascular Endothelial Growth Factor Receptors]] (VEGFRs) to accelerate angiogenesis and vasculogenesis. Accelerated angiogenesis creates the overly developed blood vessel system common to all tumors, providing oxygen and nutrients to the prodigal tumors. Bevacizumab binds to VEGF, preventing it from interacting with VEGFR, thus halting accelerated angiogenesis in tumors, preventing the cancer from growing rapidly.<ref>PMID:11815711</ref>
-Rivastigmine is an [[Acetylcholinesterase]] (AChE) inhibitor. It binds to the active site of <scene name='Rivastigmine/Acetylcholinesterase/1'>AChE</scene>, utilizing many of the same residues which bind and break down acetylcholine. By inhibiting AChE, the important neurotransmitter, [[acetylcholine]], is degraded at a slower rate, helping reverse the marked decrease in neuronal function evident in [[Alzheimer's Disease]] patients. Rivastigmine is rapidly metabolized into its principal components (carbamyl and NAP moieties) which are powerful Acetylcholine inhibitors. These components primarily <scene name='Rivastigmine/Bound/1'>primarily interact with residues</scene> GLy 117, Gly 118, Gly 119 Ala 201, Trp 233, Phe 290, Trp 84, Phe 330, His 440, & Phe 288 in tightly binding to the AChE binding site via pi stacking and hydrogen bond interactions. Rivastigmine outcompetes acetylcholine for the active site of AChE, inhibiting the esterase<ref>PMID:11888271</ref>
 ===Pharmacokinetics===
-{| class="wikitable" border="1" width="40%" style="text-align:center"
+{| class="wikitable" border="1" width="30%" style="text-align:center"
 |-
-!  colspan="2" align="center"| VEGF Inhibitor [[Pharmaceutical_Drugs#Pharmacokinetics_Translated|Pharmacokinetics]]
+!  colspan="2" align="center"| VEGF Inhibitor [[Pharmacokinetics]]<ref>PMID:17093010</ref>
 |-
 ! Parameter
 ! [[Bevacizumab]]
 |-
-! [[Pharmaceutical_Drugs#Tmax|T<sub>max</sub>]] (hr)
+! [[Pharmacokinetics#Tmax|T<sub>max</sub>]] (hr)
 ! 5.17
 |-
-! [[Pharmaceutical_Drugs#Cmax|C<sub>max</sub>]] (ng/ml)
+! [[Pharmacokinetics#Cmax|C<sub>max</sub>]] (ng/ml)
-! 248.5
+! 284000
 |-
-! [[Pharmaceutical_Drugs#Bioavailability_.28F.29|Bioavailability]] (%)
+! [[Pharmacokinetics#Bioavailability_.28F.29|Bioavailability]] (%)
-! [[Bevacizumab]]
+! 100
-|-
-! [[Pharmaceutical_Drugs#Protein_Binding|Protein Binding]] (%)
-! [[Bevacizumab]]
 |-
-! [[Pharmaceutical_Drugs#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
+! [[Pharmacokinetics#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (days)
-! 15.3
+! 20
 |-
-! [[Pharmaceutical_Drugs#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
+! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29|AUC]] (ug/ml/hr)
-! 133208
+! 97488
 |-
-! [[Pharmaceutical_Drugs#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM)
+! [[Pharmacokinetics#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM)
-! [[Bevacizumab]]
+! .9
 |-
-! [[Pharmaceutical_Drugs#Clearance_.28Cl.29|Clearance]] (L/h)
+! [[Pharmacokinetics#Clearance_.28Cl.29|Clearance]] (L/h)
-! .0086
+! .0096
 |-
 ! Dosage (mg/kg)
 ! 10
-|-
-! Metabolism
-! [[Bevacizumab]]
 |}
+</StructureSection>
 ===References===
 <references/>
 __NOEDITSECTION__
 __NOTOC__