Endoxifen

Endoxifen
Clinical data
Trade names	Zonalta
Other names	4-Hydroxy-N-desmethyltamoxifen; Desmethylhydroxytamoxifen
Routes of; administration	By mouth
Identifiers
	IUPAC name 4-[1-[4-[2-(methylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol;
CAS Number	112093-28-4 ; 114828-90-9 (E-isomer); 1032008-74-4 (hydrochloride);
PubChem CID	130621;
UNII	46AF8680RC;
ChEMBL	ChEMBL1949791;
PDB ligand	9XY (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID80149880 ;
ECHA InfoCard	100.208.548
Chemical and physical data
Formula	C25H27NO2
Molar mass	373.496 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCC(=C(C1=CC=C(C=C1)O)C2=CC=C(C=C2)OCCNC)C3=CC=CC=C3;
	InChI InChI=1S/C25H27NO2/c1-3-24(19-7-5-4-6-8-19)25(20-9-13-22(27)14-10-20)21-11-15-23(16-12-21)28-18-17-26-2/h4-16,26-27H,3,17-18H2,1-2H3; Key:MHJBZVSGOZTKRH-UHFFFAOYSA-N;

Endoxifen, also known as 4-hydroxy-N-desmethyltamoxifen, is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group as well as a protein kinase C (PKC) inhibitor. It is under development for the treatment of estrogen receptor-positive breast cancer and for the treatment of mania in bipolar disorder.^[1]^[2] It is taken by mouth.^[2]

Endoxifen is an active metabolite of tamoxifen and has been found to be effective in patients that have failed previous hormonal therapies (tamoxifen, aromatase inhibitors, and fulvestrant). ^[3]^[4]^[5] The prodrug tamoxifen is metabolized by the CYP2D6 enzyme to produce endoxifen and afimoxifene (4-hydroxytamoxifen).^[6]

Currently, endoxifen is approved by Drugs Controller General of India for the acute treatment of manic episode with or without mixed features of Bipolar I disorder.^[7] It is manufactured and sold by Intas Pharmaceuticals under the brand name Zonalta.^[8]

^ "Z-endoxifen hydrochloride". NCI Drug Dictionary.
^ ^a ^b "Endoxifen - Intas Pharmaceuticals/Jina pharmaceuticals - AdisInsight".
^
Hawse JR, Subramaniam M, Cicek M, Wu X, Gingery A, Grygo SB, et al. (2013). "Endoxifen's molecular mechanisms of action are concentration dependent and different than that of other anti-estrogens". PLOS ONE. 8 (1): e54613. Bibcode:2013PLoSO...854613H. doi:10.1371/journal.pone.0054613. PMC 3557294. PMID 23382923.
- Lay summary in: Ericson J (December 12, 2013). "New Breast Cancer Drug Endoxifen Shows Promise In Patients Resistant To Conventional Hormonal Therapy". Medical Daily.
^ Wu X, Hawse JR, Subramaniam M, Goetz MP, Ingle JN, Spelsberg TC (March 2009). "The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells". Cancer Research. 69 (5): 1722–7. doi:10.1158/0008-5472.CAN-08-3933. PMID 19244106.
^ Gingery A, Subramaniam M, Pitel KS, Reese JM, Cicek M, Lindenmaier LB, et al. (2014). "The effects of a novel hormonal breast cancer therapy, endoxifen, on the mouse skeleton". PLOS ONE. 9 (5): e98219. Bibcode:2014PLoSO...998219G. doi:10.1371/journal.pone.0098219. PMC 4031133. PMID 24853369.
^ Wilcken N (2016). "Breast cancer: a disease of subtypes". Cancer Forum. 40 (3). Archived from the original on 2016-12-03. Retrieved 2016-11-12.
^ "List of new drugs approved in the year 2019 till date" (PDF). Central Drugs Standard Control Organisation. 1 October 2021. p. 4.
^ "Drug Fact Sheet - Zonalta" (PDF). Intas Pharmaceuticals. 1 October 2021.

[1] "Z-endoxifen hydrochloride". NCI Drug Dictionary.

[AdisInsight-2] "Endoxifen - Intas Pharmaceuticals/Jina pharmaceuticals - AdisInsight".

[3] Hawse JR, Subramaniam M, Cicek M, Wu X, Gingery A, Grygo SB, et al. (2013). "Endoxifen's molecular mechanisms of action are concentration dependent and different than that of other anti-estrogens". PLOS ONE. 8 (1): e54613. Bibcode:2013PLoSO...854613H. doi:10.1371/journal.pone.0054613. PMC 3557294. PMID 23382923.
Lay summary in: Ericson J (December 12, 2013). "New Breast Cancer Drug Endoxifen Shows Promise In Patients Resistant To Conventional Hormonal Therapy". Medical Daily.

[4] Lay summary in: Ericson J (December 12, 2013). "New Breast Cancer Drug Endoxifen Shows Promise In Patients Resistant To Conventional Hormonal Therapy". Medical Daily.

[4] Wu X, Hawse JR, Subramaniam M, Goetz MP, Ingle JN, Spelsberg TC (March 2009). "The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells". Cancer Research. 69 (5): 1722–7. doi:10.1158/0008-5472.CAN-08-3933. PMID 19244106.

[5] Gingery A, Subramaniam M, Pitel KS, Reese JM, Cicek M, Lindenmaier LB, et al. (2014). "The effects of a novel hormonal breast cancer therapy, endoxifen, on the mouse skeleton". PLOS ONE. 9 (5): e98219. Bibcode:2014PLoSO...998219G. doi:10.1371/journal.pone.0098219. PMC 4031133. PMID 24853369.

[6] Wilcken N (2016). "Breast cancer: a disease of subtypes". Cancer Forum. 40 (3). Archived from the original on 2016-12-03. Retrieved 2016-11-12.

[:0-7] "List of new drugs approved in the year 2019 till date" (PDF). Central Drugs Standard Control Organisation. 1 October 2021. p. 4.

[:1-8] "Drug Fact Sheet - Zonalta" (PDF). Intas Pharmaceuticals. 1 October 2021.

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