Droloxifene

Droloxifene
Clinical data
Other names	FK-435; ICI-79280; K-060; K-21060E; RP-60850; 3-Hydroxytamoxifen; 3-OH-TAM
Routes of; administration	Oral
Pharmacokinetic data
Elimination half-life	19–37 hours
Identifiers
	IUPAC name 3-[(E)-1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol;
CAS Number	82413-20-5;
PubChem CID	3033767;
ChemSpider	2298372;
UNII	0M67U6Z98F;
KEGG	D03911;
ChEBI	CHEBI:34731;
ChEMBL	ChEMBL487;
CompTox Dashboard (EPA)	DTXSID9022441 ;
ECHA InfoCard	100.102.640
Chemical and physical data
Formula	C26H29NO2
Molar mass	387.523 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC/C(=C(/C1=CC=C(C=C1)OCCN(C)C)\C2=CC(=CC=C2)O)/C3=CC=CC=C3;
	InChI InChI=1S/C26H29NO2/c1-4-25(20-9-6-5-7-10-20)26(22-11-8-12-23(28)19-22)21-13-15-24(16-14-21)29-18-17-27(2)3/h5-16,19,28H,4,17-18H2,1-3H3/b26-25+; Key:ZQZFYGIXNQKOAV-OCEACIFDSA-N;

Droloxifene (INN, USAN) (former developmental code names FK-435, ICI-79280, K-060, K-21060E, RP-60850), also known as 3-hydroxytamoxifen, is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group^[1] that was developed originally in Germany and later in Japan for the treatment of breast cancer, osteoporosis in men and postmenopausal women, and cardiovascular disorders but was abandoned and never marketed.^[3]^[4]^[5]^[6] It reached phase II and phase III clinical trials for these indications before development was discontinued in 2000.^[6]^[7] The drug was found to be significantly less effective than tamoxifen in the treatment of breast cancer in two phase III clinical trials.^[7]^[8]

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Droloxifene is an analogue of tamoxifen, specifically 3-hydroxytamoxifen, but has been said to have 10- to 60-fold increased affinity for the estrogen receptor^[9] and reduced partial estrogen agonistic activity.^[5]^[10] The affinity of droloxifene for the estrogen receptor ranges from 0.2 to 15.2% relative to estradiol in different studies.^[11] For comparison, the ranges are 0.06 to 16% for tamoxifen and 0.1 to 12% for clomifene.^[11] Droloxifene causes a dose-dependent decrease in luteinizing hormone and follicle-stimulating hormone levels, indicating that it has antigonadotropic activity, and dose-dependently increases sex hormone-binding globulin levels, indicating that it has estrogenic activity in the liver.^[2] Similarly to tamoxifen, droloxifene has partial estrogenic effects in the uterus.^[12] Unlike tamoxifen, droloxifene does not produce DNA adduct or liver tumors in animals.^[2]

Afimoxifene (4-hydroxytamoxifen)
Endoxifen (N-desmethyl-4-hydroxytamoxifen)

[1]
Oettel M, Schillinger E (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. pp. 158, 299. ISBN 978-3-642-60107-1.
[2]
Manni A (15 January 1999). Endocrinology of Breast Cancer. Springer Science & Business Media. pp. 298–. ISBN 978-1-59259-699-7.
[3]
Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 472–. ISBN 978-1-4757-2085-3.
[4]
Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 106–. ISBN 978-0-7514-0499-9.
[5]
Jordan VC, Furr BJ (5 February 2010). Hormone Therapy in Breast and Prostate Cancer. Springer Science & Business Media. pp. 200–. ISBN 978-1-59259-152-7.
[6]
"Droloxifene". AdisInsight. Springer Nature Switzerland AG.
[7]
Ottow E, Weinmann H (8 September 2008). Nuclear Receptors as Drug Targets. John Wiley & Sons. pp. 153–. ISBN 978-3-527-62330-3.
[8]
Devita VT, Hellman S, Rosenberg SA (1 April 2003). Progress in Oncology 2003. Jones & Bartlett Learning. pp. 217–. ISBN 978-0-7637-2064-3.
[9]
Missailidis S (13 October 2008). Anticancer Therapeutics. John Wiley & Sons. pp. 165–. ISBN 978-0-470-69703-0.
[10]
Grese TA, Dodge JA (February 1998). "Selective estrogen receptor modulators (SERMs)". Current Pharmaceutical Design. 4 (1): 71–92 (76). doi:10.2174/138161280401221007111005. PMID 10197034. S2CID 40919336.
[11]
Wittliff JL, Kerr DA II, Andres SA (2005). "Estrogens IV: Estrogen-Like Pharmaceuticals". In Wexler, P. (ed.). Encyclopedia of Toxicology, 2nd Edition. Vol. Dib–L. Elsevier. pp. 254–258. ISBN 978-0-08-054800-5.
[12]
Morrow M, Jordan VC (2003). Managing Breast Cancer Risk. PMPH-USA. pp. 193–. ISBN 978-1-55009-260-8.

Droloxifene - AdisInsight

[OettelSchillinger2012-1] [1]
Oettel M, Schillinger E (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. pp. 158, 299. ISBN 978-3-642-60107-1.

[Manni1999-2] [2]
Manni A (15 January 1999). Endocrinology of Breast Cancer. Springer Science & Business Media. pp. 298–. ISBN 978-1-59259-699-7.

[Elks2014-3] [3]
Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 472–. ISBN 978-1-4757-2085-3.

[MortonHall1999-4] [4]
Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 106–. ISBN 978-0-7514-0499-9.

[CRAIGFurr2010-5] [5]
Jordan VC, Furr BJ (5 February 2010). Hormone Therapy in Breast and Prostate Cancer. Springer Science & Business Media. pp. 200–. ISBN 978-1-59259-152-7.

[AdisInsight-6] [6]
"Droloxifene". AdisInsight. Springer Nature Switzerland AG.

[OttowWeinmann2008-7] [7]
Ottow E, Weinmann H (8 September 2008). Nuclear Receptors as Drug Targets. John Wiley & Sons. pp. 153–. ISBN 978-3-527-62330-3.

[DevitaHellman2003-8] [8]
Devita VT, Hellman S, Rosenberg SA (1 April 2003). Progress in Oncology 2003. Jones & Bartlett Learning. pp. 217–. ISBN 978-0-7637-2064-3.

[Missailidis2008-9] [9]
Missailidis S (13 October 2008). Anticancer Therapeutics. John Wiley & Sons. pp. 165–. ISBN 978-0-470-69703-0.

[Grese_1998-10] [10]
Grese TA, Dodge JA (February 1998). "Selective estrogen receptor modulators (SERMs)". Current Pharmaceutical Design. 4 (1): 71–92 (76). doi:10.2174/138161280401221007111005. PMID 10197034. S2CID 40919336.

[WittliffKerr2005-11] [11]
Wittliff JL, Kerr DA II, Andres SA (2005). "Estrogens IV: Estrogen-Like Pharmaceuticals". In Wexler, P. (ed.). Encyclopedia of Toxicology, 2nd Edition. Vol. Dib–L. Elsevier. pp. 254–258. ISBN 978-0-08-054800-5.

[MorrowJordan2003-12] [12]
Morrow M, Jordan VC (2003). Managing Breast Cancer Risk. PMPH-USA. pp. 193–. ISBN 978-1-55009-260-8.

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See also

References

External links

Clinical data

Other names	FK-435; ICI-79280; K-060; K-21060E; RP-60850; 3-Hydroxytamoxifen; 3-OH-TAM
Routes of administration	Oral
Pharmacokinetic data
Elimination half-life	19–37 hours^[1]^[2]
Identifiers
IUPAC name 3-[(E)-1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol
CAS Number	82413-20-5
PubChem CID	3033767
ChemSpider	2298372
UNII	0M67U6Z98F
KEGG	D03911
ChEBI	CHEBI:34731
ChEMBL	ChEMBL487
CompTox Dashboard (EPA)	DTXSID9022441
ECHA InfoCard	100.102.640
Chemical and physical data
Formula	C₂₆H₂₉NO₂
Molar mass	387.523 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC/C(=C(/C1=CC=C(C=C1)OCCN(C)C)\C2=CC(=CC=C2)O)/C3=CC=CC=C3
InChI InChI=1S/C26H29NO2/c1-4-25(20-9-6-5-7-10-20)26(22-11-8-12-23(28)19-22)21-13-15-24(16-14-21)29-18-17-27(2)3/h5-16,19,28H,4,17-18H2,1-3H3/b26-25+ Key:ZQZFYGIXNQKOAV-OCEACIFDSA-N