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

Details

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

SHOW SMILES / InChI
Structure of FULVESTRANT

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

Molecular Formula C32H47F5O3S
Molecular Weight 606.771
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

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

2002
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
Induction of the paraoxonase-1 gene expression by resveratrol.
2004 Dec
The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-specific carcinogenicity.
2004 Dec
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
Estrogen receptor alpha, but not beta, plays a major role in 17beta-estradiol-induced murine cholesterol gallstones.
2004 Jul
Oestrogen receptor beta is required for androgen-stimulated proliferation of LNCaP prostate cancer cells.
2004 Jun
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
Leptin interferes with the effects of the antiestrogen ICI 182,780 in MCF-7 breast cancer cells.
2004 Oct 1
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
Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells.
2005
Endocrinology and hormone therapy in breast cancer: selective oestrogen receptor modulators and downregulators for breast cancer - have they lost their way?
2005
Transcriptional activation of the oxytocin promoter by oestrogens uses a novel non-classical mechanism of oestrogen receptor action.
2005 Apr
Selective oestrogen receptor modulators, aromatase inhibitors and the female breast.
2005 Aug
Effect of follicle-stimulating hormone and estrogen on the expression of betaglycan messenger ribonucleic acid levels in cultured rat granulosa cells.
2005 Aug
Alternative splicing of Slo channel gene programmed by estrogen, progesterone and pregnancy.
2005 Aug 29
CHIP (carboxyl terminus of Hsc70-interacting protein) promotes basal and geldanamycin-induced degradation of estrogen receptor-alpha.
2005 Dec
Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor beta induces proliferation of endometrial stromal cells.
2005 Dec
Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR).
2005 Dec 1
ERE-independent ERalpha target genes differentially expressed in human breast tumors.
2005 Dec 21
Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells.
2005 Feb
Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays.
2005 Feb
Co-culture of primary human mammary fibroblasts and MCF-7 cells as an in vitro breast cancer model.
2005 Feb
Novel progestogenic activity of environmental endocrine disruptors in the upregulation of calbindin-D9k in an immature mouse model.
2005 Jan
Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the cytotoxic action of TNF and p53 activity.
2005 Jul 14
Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release.
2005 Jul 15
Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens.
2005 Jul-Aug
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
CSN5/Jab1 is involved in ligand-dependent degradation of estrogen receptor {alpha} by the proteasome.
2005 Jun
The estrogenic activity of synthetic progestins used in oral contraceptives enhances fatty acid synthase-dependent breast cancer cell proliferation and survival.
2005 Jun
Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor.
2005 Jun 15
[Regulation of orphan receptor ERR alpha by estrogen and progesterone in endometrial carcinoma cell line].
2005 Jun 18
Estrogen-induced loss of progesterone receptor expression in normal and malignant ovarian surface epithelial cells.
2005 Jun 23
Differential effects of estrogens and progestins on the anticoagulant tissue factor pathway inhibitor in the rat.
2005 Mar
The putative tumor suppressor deleted in malignant brain tumors 1 is an estrogen-regulated gene in rodent and primate endometrial epithelium.
2005 Mar
Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells.
2005 Mar 4
Promoting insulin secretion in pancreatic islets by means of bisphenol A and nonylphenol via intracellular estrogen receptors.
2005 May
Estrogenic effects of two derivatives of icariin on human breast cancer MCF-7 cells.
2005 Nov
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
The phytoestrogen biochaninA weakens acute cardiac allograft rejection without affecting the reproductive system.
2005 Oct
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
Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels.
2005 Oct
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
Differential effect of estrogen receptor alpha and beta agonists on the receptor for advanced glycation end product expression in human microvascular endothelial cells.
2005 Sep 30
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
Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus.
2006 May
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:51:42 GMT 2023
Edited
by admin
on Fri Dec 15 15:51:42 GMT 2023
Record UNII
22X328QOC4
Record Status Validated (UNII)
Record Version
  • Download
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
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
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
LIVERTOX NBK548072
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
NDF-RT N0000175582
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
NCI_THESAURUS C2116
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
NDF-RT N0000000168
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
WHO-ATC L02BA03
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
NDF-RT N0000175826
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
EMA ASSESSMENT REPORTS FASLODEX (AUTHORIZED: BREAST NEOPLASMS)
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
Code System Code Type Description
HSDB
7658
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
NDF-RT
N0000000145
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY Estrogen Receptor Antagonists [MoA]
DRUG CENTRAL
1255
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
DRUG BANK
DB00947
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
FDA UNII
22X328QOC4
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
RXCUI
282357
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY RxNorm
NSC
759879
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
NCI_THESAURUS
C1379
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
DAILYMED
22X328QOC4
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
SMS_ID
100000089504
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
INN
7712
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
USAN
KK-128
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
CHEBI
31638
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
CAS
129453-61-8
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
EVMPD
SUB13933MIG
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
WIKIPEDIA
FULVESTRANT
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
PUBCHEM
104741
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
RS_ITEM_NUM
1286650
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
IUPHAR
1015
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
MERCK INDEX
m5583
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY Merck Index
ChEMBL
CHEMBL1358
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
EPA CompTox
DTXSID4022369
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
MESH
C070081
Created by admin on Fri Dec 15 15:51:42 GMT 2023 , Edited by admin on Fri Dec 15 15:51:42 GMT 2023
PRIMARY
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
EP
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
Selective estrogen receptor degrader (SERD)
BINDING
IC50
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
Binding assay
IC50
METABOLIC ENZYME -> SUBSTRATE
CELL->INHIBITOR
Viablity
IC50
TARGET->DEGRADER, SELECTIVE
100% Degradation as control
EC50
TARGET->DEGRADER, SELECTIVE
Selective estrogen receptor degrader (SERD)
BINDING
IC50
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE LESS ACTIVE -> PARENT
METABOLITE -> PARENT
PARENT -> METABOLITE ACTIVE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 0.3
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 0.7
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC