It:Maraviroc

2006-12-07T18:16:19Z

2006-12-06T15:36:42Z

Ml405: /* Supplemental Project Page */

__FORCETOC__

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|NEW: This demonstrates the use of Jmol loading discrete molecule files (rather than having to paste them into the wiki page). Upload the molecule file, and invoke it as shown here. Use it for eg loading large proteins etc. Sorry about the delay in getting this working, but the cause was pretty unobvious.--[[User:Rzepa|Rzepa]] 16:07, 4 December 2006 (UTC)
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! bgcolor="cyan" |Project Number
! bgcolor="cyan" |General Keywords
|-
| bgcolor="#CCFF00" |01
| bgcolor="#CCFF00" | [[it:Lignocaine|Lignocaine (used in dentistry as a "local")]]
|-
| bgcolor="#CCFF00" |02
| bgcolor="#66FF99" | [[it:Piperine|Piperine (active ingredient of both black and white pepper)]]
|-
| bgcolor="#CCFF00" |03
| bgcolor="#CCFF00" | [[it:Rapamycin|Rapamycin (prevents transplant rejection)]]
|-
| bgcolor="#CCFF00" |04
| bgcolor="#66FF99" | [[it:Gossypol|Gossypol (male birth control)]]
|-
| bgcolor="#CCFF00" |05
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|-
| bgcolor="#CCFF00" |06
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|-
| bgcolor="#CCFF00" |07
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| bgcolor="#CCFF00" |08
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|-
| bgcolor="#CCFF00" |09
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|-
| bgcolor="#CCFF00" |10
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|-
| bgcolor="#CCFF00" |11
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|-
| bgcolor="#CCFF00" |12
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|-
| bgcolor="#CCFF00" |13
| bgcolor="#CCFF00" | [[it:h3nbh3|Ammonia-borane: H3N-BH3 (Hydrogen storage molecule?)]]
|-
| bgcolor="#CCFF00" |14
| bgcolor="#66FF99" | [[it:Methoxsalen|Methoxsalen (Treatment of psoriasis)]]
|-
| bgcolor="#CCFF00" |15
| bgcolor="#CCFF00" | [[it:Hycocine|Hyoscine (From Mandrake and Witches Henbane, pre-med before surgery)]]
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|-
| bgcolor="#CCFF00" |18
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|-
| bgcolor="#CCFF00" |21
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| bgcolor="#CCFF00" |22
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|-
|bgcolor="#CCFF00" |23
| bgcolor="#CCFF00" | [[it:Vioxx|Vioxx (treatment of osteoarthritis symptoms and pain)]]
|-
| bgcolor="#CCFF00" |24
| bgcolor="#66FF99" | [[it:Sertraline|Sertraline HCl (anti-depression)]]
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| bgcolor="#CCFF00" |25
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| bgcolor="#CCFF00" |26
| bgcolor="#66FF99" | [[it:Zithromycin|Zithromycin (anti-infective)]]
|-
| bgcolor="#CCFF00" |27
| bgcolor="#CCFF00" | [[it:Lipitor|Lipitor (Cholesterol reducing agent)]]
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----
--[[User:Rzepa|Rzepa]] 12:25, 19 October 2006 (BST)--[[User:Rzepa|Rzepa]] 08:31, 5 November 2006 (UTC)

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----
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[[R & S Phrases]]

Detailed Herceptin Mechanism of Action

2006-12-06T15:12:14Z

Ml405:

[[Image:Herceptin_product.jpg|thumb|right|Commercially available Herceptin(R)]]

==Effect on Receptor signaling==

As briefly described previously, the overexpression of HER-2 (HER2 is one of 4 trasmembrane tyrosine kinase receptors of the HER family) genes activates numerous cellular signaling pathways, including the PI3 [http://en.wikipedia.org/wiki/Kinase kinase] (PI3K) and MAP kinase ([http://en.wikipedia.org/wiki/MAPK MAPK]) cascades. The complementary binding of Herceptin molecules with the HER2 antigens have shown to reduces signaling from these pathways, and consequently promoting [http://en.wikipedia.org/wiki/Cell_cycle cell cycle] arrest during the G1 phase of cell cycle and [http://en.wikipedia.org/wiki/Apoptosis apoptosis].

==Effect on Cell cycle and Apoptosis==
The cell cycle arrest is closely regulated by the presence of cyclin-dependent kinase ([http://en.wikipedia.org/wiki/Cyclin-dependent_kinase cdk]) inhibitor p27kip1. The presence of p27kip1 in turn inhibits cyclin E/cdk2 complexes. Herceptin molecules promote cell cycle arrest by accumulating p27kip1 and also induces apoptosis.

Apoptosis is one of the main forms of programmed cell death ([http://en.wikipedia.org/wiki/Programmed_cell_death PCD]) during the cell cycle. One important function of apoptosis is to repair any damage or mutations in the DNA in response to prevent cancer developing. Herceptin has shown to reduce the size of tumour cells by either having a direct [http://en.wikipedia.org/wiki/Cytotoxic cytotoxic effect] on the tumour cells or indirectly via activation of body’s immune system to respond and suppress the tumour cells.

[[Image:Mechdetail.jpg|centre|Detailed Mechanism of Action]]

==Effect on Angiogenesis==
[http://en.wikipedia.org/wiki/Angiogenesis Angiogenesis] is the extension/formation of new blood vessels from existing ones. Tumour cells migrate and enlarge by actively taking in nutrients from blood vessels developed by the process of angiogenesis. The overexpression of HER-2 is closely linked to high level of angiogenesis -this is another evidence that HER2 is the proto-oncogene for breast cancer. Clinical trials have shown that Herceptin can lower the level of angiogenesis.

==Acknowledgement==
Thanks to Mr. Yin Wei T for finding the illustrated diagram published in the articel listed below.
==References==
1. Rita Nahtaa and Francisco J. Esteva, Herceptin: Mechanisms of action and Resistance, 2006, 232,[http://dx.doi.org DOI]: [http://dx.doi.org/10.1016/j.canlet.2005.01.041 doi:10.1016/j.canlet.2005.01.041]

It:Herceptin

2006-12-06T14:51:34Z

Ml405: /* Further Reading */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chemical header}}| '''Schematic reperesentation of Herceptin and HER2'''
|-align="center" colspan="1" bgcolor="#ffffff" |
|[[Image:Herceptin.PNG|right|Herceptin & HER2 complex]]
|- align="center"
| [[3D Herceptin|'''Click to view Herceptin 3D !Viewing by Firefox is strongly recommended!''']]
|-
|}

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
|- bgcolor = "#ffffff"
! {{chemical header}}| '''Chemical Data'''
|
|-
| [http://www.iupac.org/dhtml_home.html Systematic (IUPAC) name]
| humanized anti-HER2 antibody, 17-(4-aminobutylamino)geldanamycin immunoconjugate,
Immunoglobulin G 1 (human-mouse monoclonal rhuMab HER2 g1-chain anti-human p185c-erbB2 receptor), Trastuzumab
|-
| Molecular formula
| C6470H10012N1726O2031S42
|-
| Molecular mass
| 145531.5 g/mol
|-
| Density
| ..... g/cm3
|-
| PubMed ID
| [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12610629 12610629]
|-
| PubChem ID
| [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=736684 736684]
|-
| Melting point
| 61 °C (FAB fragment), 71 °C (whole mAb)
|-
| Boiling point
| .....
|-
| [http://www.cas.org/ CAS number]
| 180288-69-1
|-
|}

'''Herceptin''', also known as Trastuzumab, is currently the only clinically approved 1[http://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] for the treatment of Human Epidermal Growth Factor 2 (HER2)-positive [http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic metastatic breast cancer]. Up to 25% 2of women who are diagnosed with early breast cancer overexpress HER2 and herceptin works by primarily targeting the extracellular domains of HER2 receptors.

==Synthesis of Herceptin==
Herceptin:17-(4-aminobutylamino)geldanamycin immunoconjugate can be 
synthesised from the reactant: carbamic 
acid9-{4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-butyrylamino] 
-butylamino}-13-hydroxy-8,14-dimethoxy-4,10,12,16 
-tetramethyl-3,20,22-trioxo-2-aza-bicyclo[16.3.1]docosa-1(21) 
,4,6,10,18-pentaen-9-yl ester; monoclonal antibody 
with aqeous HEPES; NaCl; EDTA as reagents in dimethylsulfoxide solvent.3
[[Image:Hercreaction.jpg|centre|C40H55N5O11]]

==Mechanism of Action==
===Cause of Breast Cancer===
A significant number of changes occur in the genetic contents of cells in human body before they turn into tumour cells. Human Epidermal Growth Factor Receptor (HER2) gene is regarded as the most important [http://en.wikipedia.org/wiki/Oncogene proto-oncogene] for the development of female breast cancer. In healthy cells, there are 2 copies of HER2 genes which undergo [http://en.wikipedia.org/wiki/Transcription_%28genetics%29 transcription] to form [http://en.wikipedia.org/wiki/MRNA mRNA] in the cytoplasm and subsequently [http://en.wikipedia.org/wiki/Translation_%28genetics%29 translation] of mRNA forming a small quantity of HER2 proteins inside ribosomes (–a process called protein synthesis or gene expression). These HER2 proteins are responsible for the intercellular transmission of impulses which regulates the cell growth and division. However, the amplification (presence of more than 2 copies) of HER2 genes in abnormal cells results in the overexpression of HER2 proteins and sustained activation of cell growth/division leading to the [http://en.wikipedia.org/wiki/Metastasis metastasis] of tumour cells.
===Effect of Herceptin===
[[Image:Herc_MOA.jpg|centre|Mechanistic illustration of Herceptin blocking EGF]] 
Herceptin is a monoclonal [http://en.wikipedia.org/wiki/Antibody antibody] with 95% of its composition identical to the human proteins -the reason why it is also called humanised antibody. The antibodys' specific 3D confirmation allow them to bind to the complementary extracellular domain of HER2 proteins overexpressed on the surface of the tumour cells. The complexation of herceptin molecules with HER2 prevents any further binding of Epidermal Growth Factor (EGF) with HER2 hence stopping continual cell growth/division. 

[[Detailed Herceptin Mechanism of Action|View detailed mechanism of action]]

==Clinical significance of Herceptin==
New prognostic tests have been developed using the edivence that overexpression of HER2 protein is an early sign of breast cancer. Although the
current definitive diagnosis for breast cancer is still made by biopsy and microscopic examination of the cell sample, several ready-to-use test kits for the detection of HER2 are now available. These tests focus on the overexpression of either the HER2 cell surface receptor protein or the HER2 gene.

In fluorescence in-situ hybridisation (FISH), tissue samples are exposed to antibodies labelled with a fluorescent dye and any copies of the HER2 gene emit fluorescent signals and can be recognised by examination under a fluorescence microscope.The test is able to determine whether the cell nucleus has the usual two, or on the other hand more than two, copies of the HER2 gene.

==References==
1. N. Yaal-Hahoshen and T. Safra, Israel Medical Association Journal, 2006, 8, 416-421. 
2. J. Baselga, E. A. Perez, T. Pienkowski and R. Bell, Oncologist, 2006, 11, 4-12. 
3. Journal; Mandler, Raya; Dadachova, Ekaterina; Brechbiel, James K.; Waldmann, Thomas A.; Brechbiel, Martin W.; BMCLE8; Bioorg. Med. Chem. Lett.; EN; 10; 10; 2000; 1025 - 1028; 
4. Rita Nahtaa and Francisco J. Esteva, Herceptin: Mechanisms of action and Resistance, 2006, 232,[http://dx.doi.org DOI]: [http://dx.doi.org/10.1016/j.canlet.2005.01.041 doi:10.1016/j.canlet.2005.01.041] 
5. [http://www.rcsb.org/pdb/explore/biologyAndChemistry.do?structureId=1N8Z Herceptin Structure Information on website of Protein Data Bank]

==Further Reading==
1. [http://www.drugs.com/cons/Trastuzumab.html Prescription Drug Information for Consumers & Professionals] 
2. [https://www.ch.ic.ac.uk/wiki/index.php/It:Tamoxifen Tamoxifen]for treatment of breast cancer 
3. [http://www.guardian.co.uk/science/story/0,,1742168,00.html The Selling of a Wonder Drug],''The Guardian'', article published on Wednesday March 29, 2006

2006-10-23T21:29:17Z

Ml405: pics added

[[Image:Herceptin_product.jpg|thumb|right|Commercially available Herceptin(R)]]

==Effect on receptor signaling==

As briefly described previously, the overexpression of HER-2 genes activates numerous cellular signaling pathways, including the PI3 kinase (PI3K) and MAP kinase (MAPK) cascades. The complementary binding of Herceptin molecules with the HER2 antigens have shown to reduces signaling from these pathways, and consequently promoting cell cycle arrest during the G1 phase of cell cycle and apoptosis.

==Effect on Cell cycle and Apoptosis==
The cell cycle arrest is closely regulated by the presence of cyclin-dependent kinase (cdk) inhibitor p27kip1. The presence of p27kip1 in turn inhibits cyclin E/cdk2 complexes which control . Herceptin molecules promotes cell cycle arrest by accumulating p27kip1 and also induces apoptosis.

Apoptosis is one of the main forms of programmed cell death (PCD) during the cell cycle. One important function of apoptosis is to repair any damage or mutations in the DNA in response to prevent cancer developing. Herceptin has shown to reduce the size of tumour cells by either having a direct cytotoxic effect on the tumour cells or indirectly triggering the body’s immune system to respond and suppress the tumour cells.

[[Image:Mechdetail.jpg|thumb|centre|Detailed Mechanism of Action]]

==Effect on Angiogenesis==

Angiogenesis is the extension/formation of new blood vessels from existing ones. Tumour cells migrate and enlarge by actively taking in nutrients from blood vessels developed by the process of angiogenesis. The overexpression of HER-2 is closely linked to raised level of angiogenesis -another evidence that HER2 is the proto-oncogene for breast cancer.

==References==

Detailed Herceptin Mechanism of Action

2006-10-23T21:28:02Z

Ml405:

[[Image:Herceptin_product.jpg|thumb|right|Commercially available Herceptin(R)]]

==Effect on receptor signaling==

As briefly described previously, the overexpression of HER-2 genes activates numerous cellular signaling pathways, including the PI3 kinase (PI3K) and MAP kinase (MAPK) cascades. The complementary binding of Herceptin molecules with the HER2 antigens have shown to reduces signaling from these pathways, and consequently promoting cell cycle arrest during the G1 phase of cell cycle and apoptosis.

==Effect on Cell cycle and Apoptosis==
The cell cycle arrest is closely regulated by the presence of cyclin-dependent kinase (cdk) inhibitor p27kip1. The presence of p27kip1 in turn inhibits cyclin E/cdk2 complexes which control . Herceptin molecules promotes cell cycle arrest by accumulating p27kip1 and also induces apoptosis.

Apoptosis is one of the main forms of programmed cell death (PCD) during the cell cycle. One important function of apoptosis is to repair any damage or mutations in the DNA in response to prevent cancer developing. Herceptin has shown to reduce the size of tumour cells by either having a direct cytotoxic effect on the tumour cells or indirectly triggering the body’s immune system to respond and suppress the tumour cells.

==Effect on Angiogenesis==

Angiogenesis is the extension/formation of new blood vessels from existing ones. Tumour cells migrate and enlarge by actively taking in nutrients from blood vessels developed by the process of angiogenesis. The overexpression of HER-2 is closely linked to raised level of angiogenesis -another evidence that HER2 is the proto-oncogene for breast cancer.

==References==

File:Mechdetail.jpg

2006-10-23T21:08:29Z

Ml405:

File:Herceptin product.jpg

2006-10-23T21:07:42Z

Ml405:

Detailed Herceptin Mechanism of Action

2006-10-23T21:04:37Z

Ml405:

==Effect on receptor signaling==

As briefly described previously, the overexpression of HER-2 genes activates numerous cellular signaling pathways, including the PI3 kinase (PI3K) and MAP kinase (MAPK) cascades. The complementary binding of Herceptin molecules with the HER2 antigens have shown to reduces signaling from these pathways, and consequently promoting cell cycle arrest during the G1 phase of cell cycle and apoptosis.

==Effect on Cell cycle and Apoptosis==
The cell cycle arrest is closely regulated by the presence of cyclin-dependent kinase (cdk) inhibitor p27kip1. The presence of p27kip1 in turn inhibits cyclin E/cdk2 complexes which control . Herceptin molecules promotes cell cycle arrest by accumulating p27kip1 and also induces apoptosis.

Apoptosis is one of the main forms of programmed cell death (PCD) during the cell cycle. One important function of apoptosis is to repair any damage or mutations in the DNA in response to prevent cancer developing. Herceptin has shown to reduce the size of tumour cells by either having a direct cytotoxic effect on the tumour cells or indirectly triggering the body’s immune system to respond and suppress the tumour cells.

==Effect on Angiogenesis==

Angiogenesis is the extension/formation of new blood vessels from existing ones. Tumour cells migrate and enlarge by actively taking in nutrients from blood vessels developed by the process of angiogenesis. The overexpression of HER-2 is closely linked to raised level of angiogenesis -another evidence that HER2 is the proto-oncogene for breast cancer.

==References==

2006-10-23T15:11:20Z

Ml405: /* Synthesis of Herceptin */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chemical header}}| '''Schematic reperesentation of Herceptin and HER2'''
|-align="center" colspan="1" bgcolor="#ffffff" |
|[[Image:Herceptin.PNG|thumb|right|Herceptin & HER2 complex]]
|- align="center"
| [[3D Herceptin|'''Click to view Herceptin 3D''']]
|-
|}

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
|- bgcolor = "#ffffff"
! {{chemical header}}| '''Chemical Data'''
|
|-
| [http://www.iupac.org/dhtml_home.html Systematic (IUPAC) name]
| humanized anti-HER2 antibody, 17-(4-aminobutylamino)geldanamycin immunoconjugate,
Immunoglobulin G 1 (human-mouse monoclonal rhuMab HER2 g1-chain anti-human p185c-erbB2 receptor), Trastuzumab
|-
| Molecular formula
| C6470H10012N1726O2031S42
|-
| Molecular mass
| 145531.5 g/mol
|-
| Density
| ..... g/cm3
|-
| PubMed ID
| [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12610629 12610629]
|-
| PubChem ID
| [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=736684 736684]
|-
| Melting point
| 61 °C (FAB fragment), 71 °C (whole mAb)
|-
| Boiling point
| .....
|-
| [http://www.cas.org/ CAS number]
| 180288-69-1
|-
|}

'''Herceptin''', also known as Trastuzumabis, is currently the only clinically approved 1[http://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] for the treatment of Human Epidermal Growth Factor 2 (HER2)-positive [http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic metastatic breast cancer]. Up to 25% 2of women who are diagnosed with early breast cancer overexpress HER2 and herceptin works by primarily targeting the extracellular domains of HER2 receptors.

==Synthesis of Herceptin==
Herceptin:17-(4-aminobutylamino)geldanamycin immunoconjugate can be synthesised from the reactant: carbamic 
acid 9-{4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-butyrylamino]-butylamino}-13-hydroxy-8,14-dimethoxy-4,10,12,16 
-tetramethyl-3,20,22-trioxo-2-aza-bicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl ester; monoclonal antibody 
with aqeous HEPES; NaCl; EDTA as reagents in dimethylsulfoxide solvent.3
[[Image:Hercreaction.jpg|thumb|C40H55N5O11]]

==Mechanism of Action==
A significant number of changes occur in the genetic contents of cells in human body before they turn into tumour cells. Human Epidermal Growth Factor Receptor (HER2) gene is regarded as the most important [http://en.wikipedia.org/wiki/Oncogene proto-oncogene] for the development of female breast cancer. In healthy cells, there are 2 copies of HER2 genes which undergo [http://en.wikipedia.org/wiki/Transcription_%28genetics%29 transcription] to form [http://en.wikipedia.org/wiki/MRNA mRNA] in the cytoplasm and subsequently [http://en.wikipedia.org/wiki/Translation_%28genetics%29 translation] of mRNA forming a small quantity of HER2 proteins inside ribosomes (–a process called protein synthesis or gene expression). These HER2 proteins are responsible for the intercellular transmission of impulses which regulates the cell growth and division. However, the amplification (presence of more than 2 copies) of HER2 genes in abnormal cells results in the overexpression of HER2 proteins and sustained activation of cell growth/division leading to the [http://en.wikipedia.org/wiki/Metastasis metastasis] of tumour cells.
[[Image:Herc_MOA.jpg]] 
Herceptin is a monoclonal [http://en.wikipedia.org/wiki/Antibody antibody] with 95% of its composition identical to the human proteins -the reason why it is also called humanised antibody. The antibodys' specific 3D confirmation allow them to bind to the complementary extracellular domain of HER2 proteins overexpressed on the surface of the tumour cells. The complexation of herceptin molecules with HER2 prevents any further binding of Epidermal Growth Factor (EGF) with HER2 hence stopping continual cell growth/division.

==Clinical significance of Herceptin==
New tests have been developed using the edivence that overexpression of HER2 protein is an early sign of breast cancer. Although the
current definitive diagnosis for breast cancer is still made by biopsy and microscopic examination of the cell sample, several ready-to-use test kits for the detection of HER2 are now available. These tests focus on the overexpression of either the HER2 cell surface receptor protein or the HER2 gene.

In fluorescence in-situ hybridisation (FISH), tissue samples are exposed to antibodies labelled with a fluorescent dye and any copies of the HER2 gene emit fluorescent signals and can be recognised by examination under a fluorescence microscope.The test is able to determine whether the cell nucleus has the usual two, or on the other hand more than two, copies of the HER2 gene.

==References==
1. N. Yaal-Hahoshen and T. Safra, Israel Medical Association Journal, 2006, 8, 416-421. 
2. J. Baselga, E. A. Perez, T. Pienkowski and R. Bell, Oncologist, 2006, 11, 4-12. 
3. Journal; Mandler, Raya; Dadachova, Ekaterina; Brechbiel, James K.; Waldmann, Thomas A.; Brechbiel, Martin W.; BMCLE8; Bioorg. Med. Chem. Lett.; EN; 10; 10; 2000; 1025 - 1028; 

==Further Reading==
1. [http://www.drugs.com/cons/Trastuzumab.html Prescription Drug Information for Consumers & Professionals]

It:Herceptin

2006-10-23T15:05:33Z

Ml405: /* Synthesis of Herceptin */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chemical header}}| '''Schematic reperesentation of Herceptin and HER2'''
|-align="center" colspan="1" bgcolor="#ffffff" |
|[[Image:Herceptin.PNG|thumb|right|Herceptin & HER2 complex]]
|- align="center"
| [[3D Herceptin|'''Click to view Herceptin 3D''']]
|-
|}

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
|- bgcolor = "#ffffff"
! {{chemical header}}| '''Chemical Data'''
|
|-
| [http://www.iupac.org/dhtml_home.html Systematic (IUPAC) name]
| humanized anti-HER2 antibody, 17-(4-aminobutylamino)geldanamycin immunoconjugate,
Immunoglobulin G 1 (human-mouse monoclonal rhuMab HER2 g1-chain anti-human p185c-erbB2 receptor), Trastuzumab
|-
| Molecular formula
| C6470H10012N1726O2031S42
|-
| Molecular mass
| 145531.5 g/mol
|-
| Density
| ..... g/cm3
|-
| PubMed ID
| [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=12610629 12610629]
|-
| PubChem ID
| [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=736684 736684]
|-
| Melting point
| 61 °C (FAB fragment), 71 °C (whole mAb)
|-
| Boiling point
| .....
|-
| [http://www.cas.org/ CAS number]
| 180288-69-1
|-
|}

'''Herceptin''', also known as Trastuzumabis, is currently the only clinically approved 1[http://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] for the treatment of Human Epidermal Growth Factor 2 (HER2)-positive [http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic metastatic breast cancer]. Up to 25% 2of women who are diagnosed with early breast cancer overexpress HER2 and herceptin works by primarily targeting the extracellular domains of HER2 receptors.

==Synthesis of Herceptin==
Herceptin:17-(4-aminobutylamino)geldanamycin immunoconjugate can be synthesised from the reactant: [[Image:Hercreaction.jpg|thumb|C40H55N5O11]] carbamic
acid 19-{4-[4-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-butyrylamino]-butylamino}-13-hydroxy-8,14-dimethoxy-4,10,12,16 
-tetramethyl-3,20,22-trioxo-2-aza-bicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl ester; monoclonal antibody 
with aqeous HEPES; NaCl; EDTA as reagents in dimethylsulfoxide solvent.3

==Mechanism of Action==
A significant number of changes occur in the genetic contents of cells in human body before they turn into tumour cells. Human Epidermal Growth Factor Receptor (HER2) gene is regarded as the most important [http://en.wikipedia.org/wiki/Oncogene proto-oncogene] for the development of female breast cancer. In healthy cells, there are 2 copies of HER2 genes which undergo [http://en.wikipedia.org/wiki/Transcription_%28genetics%29 transcription] to form [http://en.wikipedia.org/wiki/MRNA mRNA] in the cytoplasm and subsequently [http://en.wikipedia.org/wiki/Translation_%28genetics%29 translation] of mRNA forming a small quantity of HER2 proteins inside ribosomes (–a process called protein synthesis or gene expression). These HER2 proteins are responsible for the intercellular transmission of impulses which regulates the cell growth and division. However, the amplification (presence of more than 2 copies) of HER2 genes in abnormal cells results in the overexpression of HER2 proteins and sustained activation of cell growth/division leading to the [http://en.wikipedia.org/wiki/Metastasis metastasis] of tumour cells.
[[Image:Herc_MOA.jpg]] 
Herceptin is a monoclonal [http://en.wikipedia.org/wiki/Antibody antibody] with 95% of its composition identical to the human proteins -the reason why it is also called humanised antibody. The antibodys' specific 3D confirmation allow them to bind to the complementary extracellular domain of HER2 proteins overexpressed on the surface of the tumour cells. The complexation of herceptin molecules with HER2 prevents any further binding of Epidermal Growth Factor (EGF) with HER2 hence stopping continual cell growth/division.

==Clinical significance of Herceptin==
New tests have been developed using the edivence that overexpression of HER2 protein is an early sign of breast cancer. Although the
current definitive diagnosis for breast cancer is still made by biopsy and microscopic examination of the cell sample, several ready-to-use test kits for the detection of HER2 are now available. These tests focus on the overexpression of either the HER2 cell surface receptor protein or the HER2 gene.

In fluorescence in-situ hybridisation (FISH), tissue samples are exposed to antibodies labelled with a fluorescent dye and any copies of the HER2 gene emit fluorescent signals and can be recognised by examination under a fluorescence microscope.The test is able to determine whether the cell nucleus has the usual two, or on the other hand more than two, copies of the HER2 gene.

==References==
1. N. Yaal-Hahoshen and T. Safra, Israel Medical Association Journal, 2006, 8, 416-421. 
2. J. Baselga, E. A. Perez, T. Pienkowski and R. Bell, Oncologist, 2006, 11, 4-12. 
3. Journal; Mandler, Raya; Dadachova, Ekaterina; Brechbiel, James K.; Waldmann, Thomas A.; Brechbiel, Martin W.; BMCLE8; Bioorg. Med. Chem. Lett.; EN; 10; 10; 2000; 1025 - 1028; 

==Further Reading==
1. [http://www.drugs.com/cons/Trastuzumab.html Prescription Drug Information for Consumers & Professionals]