Hello, I need to use Tamoxifen in vitro. Sigma offers (Z)-4-Hydroxytamoxifen (http://www.sigmaaldrich.com/catalog/product/sigma/h7904?lang=en®ion=IT) which is described as the active metabolite. Selleck offers Endoxifen Hcl (http://www.selleckchem.com/datasheet/endoxifen-hcl-DataSheet.html) which is also presented as active metabolite. Can I be sure that they both in this case talk about the Z- configuration and exactly the same product ? I confronted the molecular structures, and there is only at the end on the left site (Methyl group and amid group) a difference in the way that they are the oppisite, but I do not remember if this is about the Z- configuration .....
Dear Vanessa,
There are exactly the same; the Z isomer.
Hoping this will be helpful,
Rafik
@Rafik
on what do you base this ? The shown structure looks the same, but after also contacting the technical service they confirmed me that Endoxifen is NOT the same as Tamoxin. application are the same but mechanism of action cannot be considered the same, they referred to : http://cancerres.aacrjournals.org/content/69/5/1722.long
A chemist told me to confront the CAS - numbers....which are different for the products. ... so I dont really understand, but seems that they are different substances
Dear Vanessa,
The structures you provided in the two links are the same with Z conformation.
Rafik
Dear Vanessa,
However, one has an extra methyl on the nitrogen ((Z)-4-Hydroxytamoxifen). Therefore, it is expected that they will have different activity.
Rafik
Yes, thats what I meant.
Maybe one more question.... if I get the Tamoxifen from Sellek, which provides a) Tamoxifen citrate and b) the free base.... which I think is OT the same than the 4OH Tamoxifen, right? Could I still use it in vtiro even if not the metabolic active form ? Or wouldn't this represent physiological circumstances as maybe in the body the Tamoxifen is metabolised by normal cells, before reaching cancer cells and in my studies then it would be exposed immediatly to the cancer cells, which might have altered protein function for the responsible metabolic pathway..... ? I'm not sure whether my thoughts make sense....
Thanks a lot
Hello Vanessa S.
You are right.
Effects and side effects of tamoxin are the sum of tamoxifen and all its metabolites. Endoxifen is an active metabolite that contribute significantly to the effectiveness of tamoxifen. Tamoxifen is metabolized via CYP2D6 into endoxifen and drugs that inhibit CYP2D6 may lead to reduced plasma concentrations of endoxifen, as you can see in the link below:
http://emedicine.medscape.com/article/1762071-overview
However, there are studies in vitro that use endoxifen, although other metabolites may be better. I will leave also a link below to an article that may answer to your questions and they make a lot of sense for me, and according to your research you may find the answer
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395096/
(The Active Tamoxifen Metabolite Endoxifen (4OHNDtam) Strongly Down-Regulates Cytokeratin 6 (CK6) in MCF-7 Breast Cancer Cells)
Hope it helps a little
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