N-Desmethyltamoxifen

N-Desmethyltamoxifen

Clinical data
Other names	ICI-55,548; Nortamoxifen; NDMTAM
Drug class	Selective estrogen receptor modulator
Identifiers
IUPAC name 2-[4-[(Z)-1,2-Diphenylbut-1-enyl]phenoxy]-N-methylethanamine
CAS Number	31750-48-8
PubChem CID	6378383
ChemSpider	2297759
UNII	OOJ759O35C
KEGG	C16546
ChEBI	CHEBI:80554
CompTox Dashboard (EPA)	DTXSID501315924
ECHA InfoCard	100.170.899
Chemical and physical data
Formula	C25H27NO
Molar mass	357.497 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC/C(=C(\C1=CC=CC=C1)/C2=CC=C(C=C2)OCCNC)/C3=CC=CC=C3
InChI InChI=1S/C25H27NO/c1-3-24(20-10-6-4-7-11-20)25(21-12-8-5-9-13-21)22-14-16-23(17-15-22)27-19-18-26-2/h4-17,26H,3,18-19H2,1-2H3/b25-24- Key:NYDCDZSEEAUOHN-IZHYLOQSSA-N

N-Desmethyltamoxifen (developmental code name ICI-55,548) is a major metabolite of tamoxifen, a selective estrogen receptor modulator (SERM). ^{[1] [2]} N-Desmethyltamoxifen is further metabolized into endoxifen (4-hydroxy-N-desmethyltamoxifen), which is thought to be the major active form of tamoxifen in the body. ^{[1] [2] [3]} In one study, N-desmethyltamoxifen had an affinity for the estrogen receptor of 2.4% relative to estradiol. ^[4] For comparison, tamoxifen, endoxifen, and afimoxifene (4-hydroxytamoxifen) had relative binding affinities of 2.8%, 181%, and 181%, respectively. ^[4]

References

1. Sanchez-Spitman AB, Swen JJ, Dezentje VO, Moes DJ, Gelderblom H, Guchelaar HJ (June 2019). "Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen". Expert Review of Clinical Pharmacology. 12 (6): 523–536. doi: 10.1080/17512433.2019.1610390 . PMID   31008668.
2. Klein DJ, Thorn CF, Desta Z, Flockhart DA, Altman RB, Klein TE (November 2013). "PharmGKB summary: tamoxifen pathway, pharmacokinetics". Pharmacogenet Genomics. 23 (11): 643–7. doi:10.1097/FPC.0b013e3283656bc1. PMC   4084801 . PMID   23962908.
3. Binkhorst L, Mathijssen RH, Jager A, van Gelder T (March 2015). "Individualization of tamoxifen therapy: much more than just CYP2D6 genotyping". Cancer Treat Rev. 41 (3): 289–99. doi:10.1016/j.ctrv.2015.01.002. PMID   25618289.
4. Maximov PY, McDaniel RE, Fernandes DJ, Bhatta P, Korostyshevskiy VR, Curpan RF, Jordan VC (October 2014). "Pharmacological relevance of endoxifen in a laboratory simulation of breast cancer in postmenopausal patients". J Natl Cancer Inst. 106 (10). doi:10.1093/jnci/dju283. PMC   4271116 . PMID   25258390.