Tamoxifen

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Tamoxifen  
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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.
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== Molecular mechanism of action ==
== Molecular mechanism of action ==
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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. It thus acts as an estrogen antagonists which inhibits the growth of some tumours dependent on estrogen stimulation.
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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 and N-desmethyl-4-hydroxytamoxifen.
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== Activation of ER-fusion proteins ==
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== Stability ==
== Stability ==
* distribution half-life: 7-14 hours
* distribution half-life: 7-14 hours
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* elimination half-life:5-7 days (range: 3-21 days)
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* elimination half-life: 5-7 days (range: 3-21 days)
* 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])

Revision as of 05:19, 6 April 2009

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.

Contents

Molecular mechanism of action

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 (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.

Activation of ER-fusion proteins

Stability

  • distribution half-life: 7-14 hours
  • elimination half-life: 5-7 days (range: 3-21 days)
  • elimination half-life of N-desmethyltamoxifen (major metabolite): 9-14 days

(estimates based on limited data probably from humans [1])

See also

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