Tamoxifen - Revision history

Jakob Suckale: /* Chemical data for tamoxifen */

Jakob Suckale — Tue, 07 Apr 2009 13:00:37 GMT

Chemical data for tamoxifen

←Older revision		Revision as of 13:00, 7 April 2009
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	{\| {{table}}		{\| {{table}}
	\|-		\|-
-	\| tamoxifen forumlation	+	! tamoxifen forumlation
-	\| molecular weight	+	! molecular weight
-	\| pKa'	+	! pKa'
-	\| equilibrium solubility in water at 37°C	+	! equilibrium solubility in water at 37°C
-	\| see also	+	! see also
	\|-		\|-
	\| tamoxifen free base		\| tamoxifen free base

Jakob Suckale: /* Chemical data for tamoxifen */

Jakob Suckale — Tue, 07 Apr 2009 12:59:44 GMT

Chemical data for tamoxifen

←Older revision		Revision as of 12:59, 7 April 2009
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	\| see also		\| see also
	\|-		\|-
-	\| tamoxifen	+	\| tamoxifen free base
-	\| xx g/mol	+	\| 371.51 g/mol
-	\| xx	+	\| 8.85
-	\| ~~xx mg/mL~~	+	\| <0.01% at 20ºC (insoluble in water)
-	\| [http://www.rxlist.com/cgi/generic/tamox.htm RX]	+	\| [http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=T5648&N5=SEARCH_CONCAT_PNO Sigma] [http://www.rxlist.com/cgi/generic/tamox.htm RX]
	\|-		\|-
	\| 4-hydroxytamoxifen (OHT)		\| 4-hydroxytamoxifen (OHT)
	\| 387.51 g/mol		\| 387.51 g/mol
	\| ?		\| ?
-	\| ? ~~mg/mL~~	+	\| ?
-	\| [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=449459 PubChem]	+	\| [http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=H7904&N5=SEARCH_CONCAT_PNO Sigma] [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=449459 PubChem]
	\|-		\|-
	\| tamoxifen citrate		\| tamoxifen citrate
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	\| 8.85		\| 8.85
	\| 0.5 mg/mL		\| 0.5 mg/mL
-	\| [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2733525 PubChem]	+	\| [http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=T9262&N5=SEARCH_CONCAT_PNO Sigma] [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2733525 PubChem]
	\|}		\|}

Jakob Suckale: table reworked

Jakob Suckale — Tue, 07 Apr 2009 12:46:52 GMT

table reworked

←Older revision		Revision as of 12:46, 7 April 2009
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	Tamoxifen is a common breast cancer drug (Nolvadex, Istubal, and Valodex). In molecular biology tamoxifen activates enzymes inactivated by fusion to a modified estrogen receptor (ER). This is employed, for example, in the timed activation of Cre recombinase in CreER mice.		Tamoxifen is a common breast cancer drug (Nolvadex, Istubal, and Valodex). In molecular biology tamoxifen activates enzymes inactivated by fusion to a modified estrogen receptor (ER). This is employed, for example, in the timed activation of Cre recombinase in CreER mice.

-	== Chemical data for [[tamoxifen]] ==	+	== Chemical data for tamoxifen ==

-	~~[[Image:Tamoxifen(OH).gif~~\|~~right\|thumb\|150px\|chemical structure of tamoxifen and 4-hydroxy-tamoxifen]]~~	+	{\| {{table}}
-		+
-	~~=== Tamoxifen citrate ===~~	+
-	{~~\| border=1 cellpadding=5 cellspacing=0~~	+
	\|-		\|-
		+	\| tamoxifen forumlation
	\| molecular weight		\| molecular weight
	\| pKa'		\| pKa'
	\| equilibrium solubility in water at 37°C		\| equilibrium solubility in water at 37°C
		+	\| see also
	\|-		\|-
-	\| ~~563.62~~ g/mol	+	\| tamoxifen
-	\| ~~8.85~~	+	\| xx g/mol
-	\| ~~0.5~~ mg/mL	+	\| xx
-	\|}	+	\| xx mg/mL
-	~~see~~ [http://www.rxlist.com/cgi/generic/tamox.htm] ~~and [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2733525 PubChem entry: tamoxifen citrate]~~	+	\| [http://www.rxlist.com/cgi/generic/tamox.htm RX]
-		+
-	~~=== 4-hydroxytamoxifen (OHT) ===~~	+
-	~~Tamoxifen is metabolised to 4-hydroxytamoxifen (often abbreviated OHT).~~	+
-	~~{\| border=1 cellpadding=5 cellspacing=0~~	+
-	\|-	+
-	~~\| molecular weight~~	+
-	~~\| pKa'~~	+
-	~~\| equilibrium solubility in water at 37°C~~	+
	\|-		\|-
		+	\| 4-hydroxytamoxifen (OHT)
	\| 387.51 g/mol		\| 387.51 g/mol
	\| ?		\| ?
	\| ? mg/mL		\| ? mg/mL
		+	\| [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=449459 PubChem]
		+	\|-
		+	\| tamoxifen citrate
		+	\| 563.62 g/mol
		+	\| 8.85
		+	\| 0.5 mg/mL
		+	\| [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2733525 PubChem]
	\|}		\|}
-	~~see [http://www.chemicalland21.com/lifescience/phar/TAMOXIFEN%20CITRATE.htm] and [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=449459 PubChem entry: 4-hydroxytamoxifen]~~

	== Molecular mechanism of action ==		== Molecular mechanism of action ==
		+
		+	[[Image:Tamoxifen(OH).gif\|right\|thumb\|150px\|chemical structure of tamoxifen and 4-hydroxy-tamoxifen]]

	Tamoxifen competitively binds to GPCR type and intracellular type estrogen receptors (ER). Binding to the intracellular ER on tumours and other tissue targets produces a nuclear complex that decreases DNA synthesis and inhibits estrogen effects ([http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=endocrin&part=A972&rendertype=box&id=A1246 diagram of estrogen & tamoxifen mechanism]). It thus acts as an estrogen antagonists which inhibits the growth of some tumours dependent on estrogen stimulation.		Tamoxifen competitively binds to GPCR type and intracellular type estrogen receptors (ER). Binding to the intracellular ER on tumours and other tissue targets produces a nuclear complex that decreases DNA synthesis and inhibits estrogen effects ([http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=endocrin&part=A972&rendertype=box&id=A1246 diagram of estrogen & tamoxifen mechanism]). It thus acts as an estrogen antagonists which inhibits the growth of some tumours dependent on estrogen stimulation.

-	Tamoxifen itself is a prodrug, having relatively little affinity for the estrogen receptor. It is metabolised in the liver by the cytochrome P450 to active metabolites such as 4-hydroxytamoxifen and N-desmethyl-4-hydroxytamoxifen.	+	Tamoxifen itself is a prodrug, having relatively little affinity for the estrogen receptor. It is metabolised in the liver by the cytochrome P450 to active metabolites such as 4-hydroxytamoxifen (see figure) and N-desmethyl-4-hydroxytamoxifen.

	== Activation of ER-fusion proteins ==		== Activation of ER-fusion proteins ==

Jakob Suckale: chemical data moved from tam administration

Jakob Suckale — Tue, 07 Apr 2009 12:34:27 GMT

chemical data moved from tam administration

←Older revision		Revision as of 12:34, 7 April 2009
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	Tamoxifen is a common breast cancer drug (Nolvadex, Istubal, and Valodex). In molecular biology tamoxifen activates enzymes inactivated by fusion to a modified estrogen receptor (ER). This is employed, for example, in the timed activation of Cre recombinase in CreER mice.		Tamoxifen is a common breast cancer drug (Nolvadex, Istubal, and Valodex). In molecular biology tamoxifen activates enzymes inactivated by fusion to a modified estrogen receptor (ER). This is employed, for example, in the timed activation of Cre recombinase in CreER mice.
		+
		+	== Chemical data for [[tamoxifen]] ==
		+
		+	[[Image:Tamoxifen(OH).gif\|right\|thumb\|150px\|chemical structure of tamoxifen and 4-hydroxy-tamoxifen]]
		+
		+	=== Tamoxifen citrate ===
		+	{\| border=1 cellpadding=5 cellspacing=0
		+	\|-
		+	\| molecular weight
		+	\| pKa'
		+	\| equilibrium solubility in water at 37°C
		+	\|-
		+	\| 563.62 g/mol
		+	\| 8.85
		+	\| 0.5 mg/mL
		+	\|}
		+	see [http://www.rxlist.com/cgi/generic/tamox.htm] and [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2733525 PubChem entry: tamoxifen citrate]
		+
		+	=== 4-hydroxytamoxifen (OHT) ===
		+	Tamoxifen is metabolised to 4-hydroxytamoxifen (often abbreviated OHT).
		+	{\| border=1 cellpadding=5 cellspacing=0
		+	\|-
		+	\| molecular weight
		+	\| pKa'
		+	\| equilibrium solubility in water at 37°C
		+	\|-
		+	\| 387.51 g/mol
		+	\| ?
		+	\| ? mg/mL
		+	\|}
		+	see [http://www.chemicalland21.com/lifescience/phar/TAMOXIFEN%20CITRATE.htm] and [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=449459 PubChem entry: 4-hydroxytamoxifen]

	== Molecular mechanism of action ==		== Molecular mechanism of action ==

Jakob Suckale: categories

Jakob Suckale — Mon, 06 Apr 2009 15:03:57 GMT

Jakob Suckale: /* Protocols using tamoxifen */

Jakob Suckale — Mon, 06 Apr 2009 09:34:01 GMT

Protocols using tamoxifen

←Older revision		Revision as of 09:34, 6 April 2009
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	== Protocols using tamoxifen ==		== Protocols using tamoxifen ==
-	* [Tamoxifen administration to mice]	+	* [[Tamoxifen administration to mice]]

	== See also ==		== See also ==

Jakob Suckale: protocols using..

Jakob Suckale — Mon, 06 Apr 2009 09:33:47 GMT

protocols using..

←Older revision		Revision as of 09:33, 6 April 2009
Line 25:		Line 25:
	* elimination half-life of N-desmethyltamoxifen (major metabolite): 9-14 days		* elimination half-life of N-desmethyltamoxifen (major metabolite): 9-14 days
	(estimates based on limited data probably from humans [http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~zDYrnM:1:bhl])		(estimates based on limited data probably from humans [http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~zDYrnM:1:bhl])
		+
		+	== Protocols using tamoxifen ==
		+	* [Tamoxifen administration to mice]

	== See also ==		== See also ==

Jakob Suckale: stability & storage

Jakob Suckale — Mon, 06 Apr 2009 09:32:09 GMT

stability & storage

←Older revision		Revision as of 09:32, 6 April 2009
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	Proteins fused to an estrogen receptor (ER) domain are sequestered by heat shock proteins (hsp). Administration of tamoxifen to an often modified ER with increased affinity for tamoxifen over the natural substrate estrogen, releases the fusion protein. In the case of an enzyme-ER fusion, like CreER, it can than act on its substrate.		Proteins fused to an estrogen receptor (ER) domain are sequestered by heat shock proteins (hsp). Administration of tamoxifen to an often modified ER with increased affinity for tamoxifen over the natural substrate estrogen, releases the fusion protein. In the case of an enzyme-ER fusion, like CreER, it can than act on its substrate.

-	== Stability ==	+	== Stability & storage ==

		+	Chemical stability (tamoxifen citrate [http://www.sigmaaldrich.com/etc/medialib/docs/Sigma/productinformationsheet2/t9262pis.Par.0001.File.tmp/t9262pis.pdf])
		+	* stable for at least 2 years when stored desiccated at 2-8°C in the dark
		+	* hygroscopic at high relative humidities
		+	* sensitive to UV light
		+
		+	Metabolism
	* distribution half-life: 7-14 hours		* distribution half-life: 7-14 hours
	* elimination half-life: 5-7 days (range: 3-21 days)		* elimination half-life: 5-7 days (range: 3-21 days)

Jakob Suckale: tamoxifen structure

Jakob Suckale — Mon, 06 Apr 2009 09:26:32 GMT

tamoxifen structure

←Older revision		Revision as of 09:26, 6 April 2009
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		+	[[Image:800px-Tamoxifen.svg.png\|right\|thumb\|200px\|chemical structure of tamoxifen]]
		+
	Tamoxifen is a common breast cancer drug (Nolvadex, Istubal, and Valodex). In molecular biology tamoxifen activates enzymes inactivated by fusion to a modified estrogen receptor (ER). This is employed, for example, in the timed activation of Cre recombinase in CreER mice.		Tamoxifen is a common breast cancer drug (Nolvadex, Istubal, and Valodex). In molecular biology tamoxifen activates enzymes inactivated by fusion to a modified estrogen receptor (ER). This is employed, for example, in the timed activation of Cre recombinase in CreER mice.

Jakob Suckale: /* Activation of ER-fusion proteins */

Jakob Suckale — Mon, 06 Apr 2009 09:21:51 GMT

Activation of ER-fusion proteins

←Older revision		Revision as of 09:21, 6 April 2009
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	== Activation of ER-fusion proteins ==		== Activation of ER-fusion proteins ==

		+	Proteins fused to an estrogen receptor (ER) domain are sequestered by heat shock proteins (hsp). Administration of tamoxifen to an often modified ER with increased affinity for tamoxifen over the natural substrate estrogen, releases the fusion protein. In the case of an enzyme-ER fusion, like CreER, it can than act on its substrate.

	== Stability ==		== Stability ==

←Older revision		Revision as of 15:03, 6 April 2009
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	* [http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=T5648\|SIGMA&N5=SEARCH_CONCAT_PNO\|BRAND_KEY&F=SPEC Tamoxifen] and [http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=T9262\|SIGMA&N5=SEARCH_CONCAT_PNO\|BRAND_KEY&F=SPEC Tamoxifen citrate datasheets] on the Sigma website		* [http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=T5648\|SIGMA&N5=SEARCH_CONCAT_PNO\|BRAND_KEY&F=SPEC Tamoxifen] and [http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=T9262\|SIGMA&N5=SEARCH_CONCAT_PNO\|BRAND_KEY&F=SPEC Tamoxifen citrate datasheets] on the Sigma website
	* [http://en.wikipedia.org/wiki/Estrogen_receptor Estrogen receptor in the Wikipedia]		* [http://en.wikipedia.org/wiki/Estrogen_receptor Estrogen receptor in the Wikipedia]
		+
		+
		+	[[Category:Material]]