FULVESTRANT

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 Search

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

Molecular Formula	C32H47F5O3S
Molecular Weight	606.7731
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 123 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26407012	Antagonist 2575		0.0631 nM [IC50]
MCF7 21 Target ID: CHEMBL387 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26407012	Inhibitor 7728		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 8043	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 1601 inhibitor 1467 inducer 707	inhibitor 1604 inducer 355	inhibitor 1702 inducer 97

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2C19 1325	UGT1A1 393 UGT1A3 397 UGT1A4 330 UGT1A8 266	CYP1A2 637 CYP2C19 269

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1532	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP1A2 1532	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2C19 1392	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2C19 1392	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2C9 1648	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2C9 1648	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2D6 1738	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP2D6 1738	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-344_Fulvestrant_biopharmr.pdf#page=21 Page: 21,22	no
CYP3A4 1772	inducer 1440 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 1772	inhibitor 3045 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 393	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/16339389/	yes
UGT1A3 397	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/16339389/	yes
UGT1A4 330	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/16339389/	yes
UGT1A8 266	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/16339389/	yes
CYP3A4 1601	substrate 3113 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
Estrogenicity of bisphenol A in a human endometrial carcinoma cell line.	1999 Apr 25	10411312
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	10433208
Effects of environmental estrogens on tumor necrosis factor alpha-mediated apoptosis in MCF-7 cells.	1999 Nov	10545406
Transcriptional activation of c-fos protooncogene by 17beta-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition.	1999 Sep	10478842
WISP-2 as a novel estrogen-responsive gene in human breast cancer cells.	2000 Aug 18	10944450
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
Activation of estrogen receptor beta is a prerequisite for estrogen-dependent upregulation of nitric oxide synthases in neonatal rat cardiac myocytes.	2001 Aug 3	11583108
Modulation of aromatase expression in human breast tissue.	2001 Dec	11850205
Inhibition of E2-induced expression of BRCA1 by persistent organochlorines.	2002	12473173
Modulation of estrogen receptor-dependent reporter construct activation and G0/G1-S-phase transition by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells.	2002 Dec	12441364
Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland.	2003 Aug	12858169
Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen.	2003 Nov	14602803
Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone.	2004 Dec 1	15557169
Augmented endothelial nitric oxide synthase (eNOS) protein expression in human pregnant myometrium: possible involvement of eNOS promoter activation by estrogen via both estrogen receptor (ER)alpha and ERbeta.	2004 Feb	14742696
Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1.	2004 Feb	14605097
Small nuclear RING finger protein expression during gonad development: regulation by gonadotropins and estrogen in the postnatal ovary.	2004 May	14749358
Xenoestrogen-induced ERK-1 and ERK-2 activation via multiple membrane-initiated signaling pathways.	2004 Nov	15531431
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
Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells.	2005	16168102
Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor beta induces proliferation of endometrial stromal cells.	2005 Dec	16020483
Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells.	2005 Feb	15539556
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	15537743
Co-culture of primary human mammary fibroblasts and MCF-7 cells as an in vitro breast cancer model.	2005 Feb	15525692
Differential effects of estrogens and progestins on the anticoagulant tissue factor pathway inhibitor in the rat.	2005 Mar	15857755
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
Estrogen receptor-alpha regulates SOCS-3 expression in human breast cancer cells.	2005 Sep 16	16055089
Glycogen synthase kinase-3 interacts with and phosphorylates estrogen receptor alpha and is involved in the regulation of receptor activity.	2005 Sep 23	16076840
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.

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:04:39 UTC 2021` Edited by `admin` on `Fri Jun 25 21:04:39 UTC 2021`
Record UNII	22X328QOC4
Record Status	`Validated (UNII)`
Record Version

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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

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