Trastuzumab
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | <applet load="" size="480" color="" frame="true" spin="on" Scene =" | + | <applet load="" size="480" color="" frame="true" spin="on" Scene ="" align="right" caption="Tastuzumab, better known as Herceptin, ([[3bdy"/> |
| - | ===Better Known as: | + | ===Better Known as: Herceptin=== |
| - | * Marketed By: | + | * Marketed By: Genentech<br /> |
| - | * Major Indication: [[ | + | * Major Indication: Breast [[Cancer]]<br /> |
| - | * Drug Class: [[ | + | * Drug Class: Human [[Epidermal Growth Factor Receptor]] 2 (HER2) Inhibitor |
| - | * Date of FDA Approval (Discontinued): | + | * Date of FDA Approval (Discontinued): 1998 (2015) <br /> |
| - | * | + | * 2008 Sales: $4.75 Billion |
| - | * Importance: It | + | * Importance: It is a very effective treatment against HER2-positive metastatic breast [[cancer]] compared to other cancer therapies. Controversial due to its cost of nearly $100,000 per year. Is often pointed to as an example of the benefits of personalized medicine in which a patent's genetic profile is used to optimize their medication regimen. |
* The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information | * The following is a list of Pharmacokinetic Parameters. See: [[Pharmaceutical Drugs]] for more information | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
When [[HIV]] first infects someone, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by [[HIV Protease]]. The subunits of <scene name='Amprenavir/Protease/1'>HIV Protease</scene> come together to form a catalytic tunnel capable of tightly binding the nascent peptides and cleaving them into their mature, infectious form. Within this tunnel lies <scene name='Amprenavir/Proteasec/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Amprenavir/Proteasecas/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Amprenavir <scene name='Amprenavir/Bound/1'>binds specifically</scene> to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their infectious form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.<ref>PMID:1799632</ref><ref>doi:10.1038/nrd1907</ref> | When [[HIV]] first infects someone, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by [[HIV Protease]]. The subunits of <scene name='Amprenavir/Protease/1'>HIV Protease</scene> come together to form a catalytic tunnel capable of tightly binding the nascent peptides and cleaving them into their mature, infectious form. Within this tunnel lies <scene name='Amprenavir/Proteasec/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Amprenavir/Proteasecas/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Amprenavir <scene name='Amprenavir/Bound/1'>binds specifically</scene> to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their infectious form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.<ref>PMID:1799632</ref><ref>doi:10.1038/nrd1907</ref> | ||
| - | |||
| - | ===Drug Resistance=== | ||
| - | The biggest difficulty with treating [[HIV]] is the rapidity at which it mutates and becomes resistant to treatments. To view a comprehensive and interactive analysis of the mutations which confer drug resistance to [[HIV Protease]], See: [[HIV Protease Inhibitor Resistance Profile]] | ||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
| Line 45: | Line 42: | ||
|- | |- | ||
! Metabolism | ! Metabolism | ||
| - | ! | + | ! Unknown |
|} | |} | ||
Revision as of 13:52, 8 December 2010
|
Better Known as: Herceptin
- Marketed By: Genentech
- Major Indication: Breast Cancer
- Drug Class: Human Epidermal Growth Factor Receptor 2 (HER2) Inhibitor
- Date of FDA Approval (Discontinued): 1998 (2015)
- 2008 Sales: $4.75 Billion
- Importance: It is a very effective treatment against HER2-positive metastatic breast cancer compared to other cancer therapies. Controversial due to its cost of nearly $100,000 per year. Is often pointed to as an example of the benefits of personalized medicine in which a patent's genetic profile is used to optimize their medication regimen.
- The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information
Mechanism of Action
When HIV first infects someone, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by HIV Protease. The subunits of come together to form a catalytic tunnel capable of tightly binding the nascent peptides and cleaving them into their mature, infectious form. Within this tunnel lies , which contain the . These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Amprenavir to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their infectious form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.[1][2]
Pharmacokinetics
| EGFR Inhibitor Pharmacokinetics[3] | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Parameter | Trastuzumab | ||||||||||
| Tmax (hr) | 1.7 | ||||||||||
| Cmax (ng/ml) | 203000 | ||||||||||
| Bioavailability (%) | |||||||||||
| T1/2 (days) | 27 | ||||||||||
| AUC (ug/ml/hr) | 45036 | ||||||||||
| Clearance (L/h) | .009 | ||||||||||
| Dosage (mg) | 250 | ||||||||||
| Metabolism | Unknown | ||||||||||
References
- ↑ Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ. The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie. 1991 Nov;73(11):1391-6. PMID:1799632
- ↑ Flexner C, Bate G, Kirkpatrick P. Tipranavir. Nat Rev Drug Discov. 2005 Dec;4(12):955-6. PMID:16370086 doi:10.1038/nrd1907
- ↑ Leyland-Jones B, Gelmon K, Ayoub JP, Arnold A, Verma S, Dias R, Ghahramani P. Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol. 2003 Nov 1;21(21):3965-71. Epub 2003 Sep 24. PMID:14507946 doi:10.1200/JCO.2003.12.109
