From Wikipedia, the free encyclopedia
Chemical compound
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]
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]
See also
References
^
a
b 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 .
^
a
b
c Manni A (15 January 1999).
Endocrinology of Breast Cancer . Springer Science & Business Media. pp. 298–.
ISBN
978-1-59259-699-7 .
^ 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 .
^ 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 .
^
a
b 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 .
^
a
b
"Droloxifene" . AdisInsight . Springer Nature Switzerland AG.
^
a
b Ottow E, Weinmann H (8 September 2008).
Nuclear Receptors as Drug Targets . John Wiley & Sons. pp. 153–.
ISBN
978-3-527-62330-3 .
^ Devita VT, Hellman S, Rosenberg SA (1 April 2003).
Progress in Oncology 2003 . Jones & Bartlett Learning. pp. 217–.
ISBN
978-0-7637-2064-3 .
^ Missailidis S (13 October 2008).
Anticancer Therapeutics . John Wiley & Sons. pp. 165–.
ISBN
978-0-470-69703-0 .
^ 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 .
^
a
b 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 .
^ Morrow M, Jordan VC (2003).
Managing Breast Cancer Risk . PMPH-USA. pp. 193–.
ISBN
978-1-55009-260-8 .
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