FULVESTRANT

Details

Stereochemistry	EPIMERIC
Molecular Formula	C32H47F5O3S
Molecular Weight	606.771
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]3([H])C4=C(C[C@@H](CCCCCCCCC[S+]([O-])CCCC(F)(F)C(F)(F)F)[C@@]23[H])C=C(O)C=C4

InChI

InChIKey=VWUXBMIQPBEWFH-WCCTWKNTSA-N

InChI=1S/C32H47F5O3S/c1-30-17-15-26-25-12-11-24(38)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-41(40)19-9-16-31(33,34)32(35,36)37/h11-12,21-22,26-29,38-39H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29-,30+,41?/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00947
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/ppa/fulvestrant.html

Fulvestrant is a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor. Fulvestrant competitively and reversibly binds to estrogen receptors present in cancer cells and achieves its anti-estrogen effects through two separate mechanisms. First, fulvestrant binds to the receptors and downregulates them so that estrogen is no longer able to bind to these receptors. Second, fulvestrant degrades the estrogen receptors to which it is bound. Both of these mechanisms inhibit the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer cell lines. Fulvestrant is used for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. Fulvestrant is marketed under the trade name Faslodex, by AstraZeneca.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26407012	Antagonist 2760		0.0631 nM [IC50]
MCF7 21 Target ID: CHEMBL387 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26407012	Inhibitor 8228		0.1 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hormone receptor positive metastatic breast cancer 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021344s015lbl.pdf	Primary		Approved 8360	FASLODEX Approved Use FASLODEX is an estrogen receptor antagonist indicated for the: Treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Launch Date 1.01753278E12

C_max

Value	Dose	Co-administered	Analyte	Population
25.1 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021344Orig1s039lbl.pdf	500 mg single, intramuscular dose: 500 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		FULVESTRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
11400 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021344Orig1s039lbl.pdf	500 mg single, intramuscular dose: 500 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		FULVESTRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
40 day DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021344Orig1s039lbl.pdf	250 mg single, intramuscular dose: 250 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		FULVESTRANT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg 1 times / month multiple, intramuscular Highest studied dose Dose: 500 mg, 1 times / month Route: intramuscular Route: multiple Dose: 500 mg, 1 times / month Sources: https://pubmed.ncbi.nlm.nih.gov/29901634	unhealthy, 54 years n = 1 Health Status: unhealthy Condition: breast cancer Age Group: 54 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29901634	Sources: https://pubmed.ncbi.nlm.nih.gov/29901634
500 mg 1 times / month multiple, intramuscular Dose: 500 mg, 1 times / month Route: intramuscular Route: multiple Dose: 500 mg, 1 times / month Sources: https://pubmed.ncbi.nlm.nih.gov/33261799	unhealthy, 56 years n = 1 Health Status: unhealthy Condition: ductal carcinoma of the breast Age Group: 56 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/33261799	Disc. AE: Epidermal necrolysis... AEs leading to discontinuation/dose reduction: Epidermal necrolysis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/33261799

AEs

AE	Significance	Dose	Population
Epidermal necrolysis	1 patient Disc. AE	500 mg 1 times / month multiple, intramuscular Dose: 500 mg, 1 times / month Route: intramuscular Route: multiple Dose: 500 mg, 1 times / month Sources: https://pubmed.ncbi.nlm.nih.gov/33261799	unhealthy, 56 years n = 1 Health Status: unhealthy Condition: ductal carcinoma of the breast Age Group: 56 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/33261799

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inhibitor 1579 inducer 768	inhibitor 1752 inducer 383	inhibitor 1837 inducer 97

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2C19 1463	UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A8 283	CYP1A2 689 CYP2C19 290

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2C19 1537	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2C9 1803	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2D6 1875	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no	weak (co-administration study) Comment: fulvestrant increased midazolam AUC by 11% but decreased Cmax by 25% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no	weak (co-administration study) Comment: fulvestrant increased midazolam AUC by 11% but decreased Cmax by 25% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A1 418	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16339389/	yes
UGT1A3 422	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16339389/	yes
UGT1A4 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16339389/	yes
UGT1A8 283	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/16339389/	yes
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21.0	yes	no (co-administration study) Comment: label: administration with rifampin (inducer) showed not effect on PK of fulvestrant Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31638	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31638
ChemicalBook	CB0698542	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0698542
Selleck Chemicals	Fulvestrant	http://www.selleckchem.com/products/Fulvestrant.html
eMolecules	6719147	https://www.emolecules.com/cgi-bin/more?vid=6719147

PubMed

Title	Date	PubMed
Superinduction of c-fos gene expression by estrogen in cultured guinea-pig endometrial cells requires priming by a cycloheximide-dependent mechanism.	1992 Sep	1505453
The aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT) heterodimer interacts with naturally occurring estrogen response elements.	1999 Nov 25	10619402
Proteinase inhibitor 9, an inhibitor of granzyme B-mediated apoptosis, is a primary estrogen-inducible gene in human liver cells.	2000 Feb 25	10681578
Molecular analysis of the inhibition of monocyte chemoattractant protein-1 gene expression by estrogens and xenoestrogens in MCF-7 cells.	2000 Jan	10614622
Effects of arsenite on estrogen receptor-alpha expression and activity in MCF-7 breast cancer cells.	2000 Oct	11014213
Effects of beta-estradiol and bisphenol A on heat shock protein levels and localization in the mouse uterus are antagonized by the antiestrogen ICI 182,780.	2001 Oct	11568360
Inhibition of E2-induced expression of BRCA1 by persistent organochlorines.	2002	12473173
Estradiol enhances and estriol inhibits the expression of CYP1A1 induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in a mouse ovarian cancer cell line.	2002 Jul 15	12093619
Triphenylethylene antiestrogen-induced acute relaxation of mouse duodenal muscle. Possible involvement of Ca2+ channels.	2002 Jun 12	12079691
Organochlorine pesticides directly regulate gonadotropin-releasing hormone gene expression and biosynthesis in the GT1-7 hypothalamic cell line.	2002 Jun 28	12088877
17-epiestriol, an estrogen metabolite, is more potent than estradiol in inhibiting vascular cell adhesion molecule 1 (VCAM-1) mRNA expression.	2003 Apr 4	12547825
Down-regulation of inducible nitric oxide synthase and tumor necrosis factor-alpha expression by bisphenol A via nuclear factor-kappaB inactivation in macrophages.	2003 Jun 30	12860292
The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes.	2003 Mar	12612060
Resveratrol acts as an estrogen receptor (ER) agonist in breast cancer cells stably transfected with ER alpha.	2003 May 1	12594813
Synthetic estrogen-mediated activation of ERK 2 intracellular signaling molecule.	2003 Oct	14710592
BMP7/ActRIIB regulates estrogen-dependent apoptosis: new biomarkers for environmental estrogens.	2004	14994273
Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation.	2004 Apr	15072547
Effects of the pesticides prochloraz and methiocarb on human estrogen receptor alpha and beta mRNA levels analyzed by on-line RT-PCR.	2004 Aug	15130599
Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells.	2004 Dec	15316697
Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials.	2004 Mar	15094759
Estrogen modulates microglial inflammatory mediator production via interactions with estrogen receptor beta.	2004 Nov	15256495
Proliferation-stimulating effects of icaritin and desmethylicaritin in MCF-7 cells.	2004 Nov 19	15541416
Leptin interferes with the effects of the antiestrogen ICI 182,780 in MCF-7 breast cancer cells.	2004 Oct 1	15475434
Development and characterization of a cell line that stably expresses an estrogen-responsive luciferase reporter for the detection of estrogen receptor agonist and antagonists.	2004 Sep	15166400
Endocrinology and hormone therapy in breast cancer: selective oestrogen receptor modulators and downregulators for breast cancer - have they lost their way?	2005	15987442
ERE-independent ERalpha target genes differentially expressed in human breast tumors.	2005 Dec 21	16298037
Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells.	2005 Feb	15539556
Novel progestogenic activity of environmental endocrine disruptors in the upregulation of calbindin-D9k in an immature mouse model.	2005 Jan	15509668
Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release.	2005 Jul 15	15950373
Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells.	2005 Jun	15930183
Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor.	2005 Jun 15	15925091
[Regulation of orphan receptor ERR alpha by estrogen and progesterone in endometrial carcinoma cell line].	2005 Jun 18	15968320
The putative tumor suppressor deleted in malignant brain tumors 1 is an estrogen-regulated gene in rodent and primate endometrial epithelium.	2005 Mar	15564322
Estrogenic effects of two derivatives of icariin on human breast cancer MCF-7 cells.	2005 Nov	16323292
Estrogen receptor alpha increases basal and cigarette smoke extract-induced expression of CYP1A1 and CYP1B1, but not GSTP1, in normal human bronchial epithelial cells.	2005 Nov	16010691
Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin.	2005 Oct	16202921
Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels.	2005 Oct	15994367
Effect of methoxychlor and estradiol on cytochrome p450 enzymes in the mouse ovarian surface epithelium.	2006 Feb	16280380
Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus.	2006 May	16467188

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Breast Cancer Initial dose: 500 mg IM on days 1, 15, and 29, then once a month thereafter.

Route of Administration: Intramuscular

In Vitro Use Guide

In human and rat mesangial cells, increased type IV collagen and fibronectin gene transcription induced by TGF-b1 was downregulated by Fulvestrant at concentrations ranging from 10(-10) M to 10(-7) M.

Name

Type

Language

FULVESTRANT

Official Name

English

FULVESTRANT [MART.]

Common Name

English

ZD-9238

Code

English

FULVESTRANT [MI]

Common Name

English

FULVESTRANT [USP-RS]

Common Name

English

FULVESTRANT [VANDF]

Common Name

English

FULVESTRANT [USP IMPURITY]

Common Name

English

Fulvestrant [WHO-DD]

Common Name

English

FASLODEX

Brand Name

English

ICI-182780

Code

English

FULVESTRANT [JAN]

Common Name

English

FULVESTRANT [ORANGE BOOK]

Common Name

English

NSC-759879

Code

English

FULVESTRANT [USP MONOGRAPH]

Common Name

English

ESTRA-1,3,5(10)-TRIENE-3,17-DIOL, 7-(9-((4,4,5,5,5-PENTAFLUOROPENTYL)SULFINYL)NONYL)-, (7.ALPHA.,17.BETA.)-

Systematic Name

English

fulvestrant [INN]

Common Name

English

ZD9238

Code

English

ICI 182,780

Code

English

FULVESTRANT [EP MONOGRAPH]

Common Name

English

FULVESTRANT [EMA EPAR]

Common Name

English

7.ALPHA.-(9-(4,4,5,5,5-PENTAFLUOROPENTYLSULPHINYL)NONYL)ESTRA-1,3,5(10)-TRIENE-3,17.BETA.-DIOL

Systematic Name

English

FULVESTRANT [USAN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QL02BA03