U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry EPIMERIC
Molecular Formula C32H47F5O3S
Molecular Weight 606.7731
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FULVESTRANT

SMILES

C[C@@]12CC[C@]3([H])c4ccc(cc4C[C@@]([H])(CCCCCCCCCS(=O)CCCC(C(F)(F)F)(F)F)[C@@]3([H])[C@]2([H])CC[C@]1([H])O)O

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
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

Curator's Comment:: Fulvestrant does not cross the blood–brain barrier

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.0631 nM [IC50]
0.1 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
25.1 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
11400 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
40 day
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

Doses

DosePopulationAdverse 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:
unhealthy, 54 years
n = 1
Health Status: unhealthy
Condition: breast cancer
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
500 mg 1 times / month multiple, intramuscular
Dose: 500 mg, 1 times / month
Route: intramuscular
Route: multiple
Dose: 500 mg, 1 times / month
Sources:
unhealthy, 56 years
n = 1
Health Status: unhealthy
Condition: ductal carcinoma of the breast
Age Group: 56 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Epidermal necrolysis...
AEs leading to
discontinuation/dose reduction:
Epidermal necrolysis (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy, 56 years
n = 1
Health Status: unhealthy
Condition: ductal carcinoma of the breast
Age Group: 56 years
Sex: F
Population Size: 1
Sources:
Overview

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
weak (co-administration study)
Comment: fulvestrant increased midazolam AUC by 11% but decreased Cmax by 25%
Page: 21,22
no
weak (co-administration study)
Comment: fulvestrant increased midazolam AUC by 11% but decreased Cmax by 25%
Page: 21,22
Drug as victim
PubMed

PubMed

TitleDatePubMed
Superinduction of c-fos gene expression by estrogen in cultured guinea-pig endometrial cells requires priming by a cycloheximide-dependent mechanism.
1992 Sep
Estrogenicity of bisphenol A in a human endometrial carcinoma cell line.
1999 Apr 25
Methoxychlor stimulates estrogen-responsive messenger ribonucleic acids in mouse uterus through a non-estrogen receptor (non-ER) alpha and non-ER beta mechanism.
1999 Aug
Effects of environmental estrogens on tumor necrosis factor alpha-mediated apoptosis in MCF-7 cells.
1999 Nov
Estrogen directly respresses gonadotropin-releasing hormone (GnRH) gene expression in estrogen receptor-alpha (ERalpha)- and ERbeta-expressing GT1-7 GnRH neurons.
1999 Nov
The aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT) heterodimer interacts with naturally occurring estrogen response elements.
1999 Nov 25
Transcriptional activation of c-fos protooncogene by 17beta-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition.
1999 Sep
WISP-2 as a novel estrogen-responsive gene in human breast cancer cells.
2000 Aug 18
Proteinase inhibitor 9, an inhibitor of granzyme B-mediated apoptosis, is a primary estrogen-inducible gene in human liver cells.
2000 Feb 25
Molecular analysis of the inhibition of monocyte chemoattractant protein-1 gene expression by estrogens and xenoestrogens in MCF-7 cells.
2000 Jan
Relative binding affinity does not predict biological response to xenoestrogens in rat endometrial adenocarcinoma cells.
2000 Oct
Effects of arsenite on estrogen receptor-alpha expression and activity in MCF-7 breast cancer cells.
2000 Oct
Activation of estrogen receptor beta is a prerequisite for estrogen-dependent upregulation of nitric oxide synthases in neonatal rat cardiac myocytes.
2001 Aug 3
Modulation of aromatase expression in human breast tissue.
2001 Dec
Transcriptional activation of heat shock protein 27 gene expression by 17beta-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists.
2001 Feb
Cell-transforming activity and estrogenicity of bisphenol-A and 4 of its analogs in mammalian cells.
2001 Jul 1
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
Infertility and testicular atrophy in the antiestrogen-treated adult male rat.
2001 Sep
Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens.
2001 Sep 14
Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer.
2001 Sep 15
Stimulation of alkaline phosphatase activity in Ishikawa cells induced by various phytoestrogens and synthetic estrogens.
2002 Dec
Effects of the environmental estrogens bisphenol A, o,p'-DDT, p-tert-octylphenol and coumestrol on apoptosis induction, cell proliferation and the expression of estrogen sensitive molecular parameters in the human breast cancer cell line MCF-7.
2002 Jan
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
Triphenylethylene antiestrogen-induced acute relaxation of mouse duodenal muscle. Possible involvement of Ca2+ channels.
2002 Jun 12
De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor.
2003 Apr 10
Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland.
2003 Aug
Modulation of antioxidant enzyme expression and function by estrogen.
2003 Jul 25
Estrogen-like activity of metals in MCF-7 breast cancer cells.
2003 Jun
Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation.
2004 Apr
Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells.
2004 Dec
Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone.
2004 Dec 1
Aryl hydrocarbon receptor-mediated inhibition of LNCaP prostate cancer cell growth and hormone-induced transactivation.
2004 Jan
The unusual binding properties of the third distinct teleost estrogen receptor subtype ERbetaa are accompanied by highly conserved amino acid changes in the ligand binding domain.
2004 Jun
Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials.
2004 Mar
Xenoestrogen-induced ERK-1 and ERK-2 activation via multiple membrane-initiated signaling pathways.
2004 Nov
Estrogen modulates microglial inflammatory mediator production via interactions with estrogen receptor beta.
2004 Nov
Proliferation-stimulating effects of icaritin and desmethylicaritin in MCF-7 cells.
2004 Nov 19
CHIP (carboxyl terminus of Hsc70-interacting protein) promotes basal and geldanamycin-induced degradation of estrogen receptor-alpha.
2005 Dec
Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells.
2005 Feb
Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity.
2005 Jul 14
Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens.
2005 Jul-Aug
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
Estrogen receptor-alpha regulates SOCS-3 expression in human breast cancer cells.
2005 Sep 16
Glycogen synthase kinase-3 interacts with and phosphorylates estrogen receptor alpha and is involved in the regulation of receptor activity.
2005 Sep 23
Effect of methoxychlor and estradiol on cytochrome p450 enzymes in the mouse ovarian surface epithelium.
2006 Feb
Characterization of estrogen receptor betab in sea bream (Sparus auratus): phylogeny, ligand-binding, and comparative analysis of expression.
2006 Jan 15
Effects of endocrine disrupters on the expression of growth hormone and prolactin mRNA in the rainbow trout pituitary.
2006 Jan 15
Patents

Sample Use Guides

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 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
EMA EPAR   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
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
FASLODEX
Brand Name English
ICI-182780
Code English
FULVESTRANT [JAN]
Common Name English
FULVESTRANT [ORANGE BOOK]
Common Name English
FULVESTRANT [WHO-DD]
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 [USP]
Common 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
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
LIVERTOX 444
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
NDF-RT N0000175582
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
NCI_THESAURUS C2116
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
NDF-RT N0000000168
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
WHO-ATC L02BA03
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
NDF-RT N0000175826
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
EMA ASSESSMENT REPORTS FASLODEX (AUTHORIZED: BREAST NEOPLASMS)
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
Code System Code Type Description
HSDB
7658
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
NDF-RT
N0000000145
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY Estrogen Receptor Antagonists [MoA]
DRUG CENTRAL
1255
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
DRUG BANK
DB00947
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
FDA UNII
22X328QOC4
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
RXCUI
282357
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C1379
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
INN
7712
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
CAS
129453-61-8
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
EVMPD
SUB13933MIG
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
WIKIPEDIA
FULVESTRANT
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
PUBCHEM
104741
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
IUPHAR
1015
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
MERCK INDEX
M5583
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL1358
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
EPA CompTox
129453-61-8
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY
USP_CATALOG
1286650
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY USP-RS
MESH
C070081
Created by admin on Fri Jun 25 21:04:39 UTC 2021 , Edited by admin on Fri Jun 25 21:04:39 UTC 2021
PRIMARY