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
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
DescriptionSources: http://www.drugbank.ca/drugs/DB00947Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/ppa/fulvestrant.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16251200
Curator's Comment: Fulvestrant does not cross the blood–brain barrier
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26407012 |
0.0631 nM [IC50] | ||
Target ID: CHEMBL387 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26407012 |
0.1 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | FASLODEX Approved UseFASLODEX 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 Date2002 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
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: |
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
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: |
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes | ||||
yes | ||||
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 |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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Estrogen directly respresses gonadotropin-releasing hormone (GnRH) gene expression in estrogen receptor-alpha (ERalpha)- and ERbeta-expressing GT1-7 GnRH neurons. | 1999 Nov |
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WISP-2 as a novel estrogen-responsive gene in human breast cancer cells. | 2000 Aug 18 |
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Molecular analysis of the inhibition of monocyte chemoattractant protein-1 gene expression by estrogens and xenoestrogens in MCF-7 cells. | 2000 Jan |
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Activation of estrogen receptor beta is a prerequisite for estrogen-dependent upregulation of nitric oxide synthases in neonatal rat cardiac myocytes. | 2001 Aug 3 |
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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 |
|
Synthetic estrogen-mediated activation of ERK 2 intracellular signaling molecule. | 2003 Oct |
|
Regulation of uterine hsp90alpha, hsp72 and HSF-1 transcription in B6C3F1 mice by beta-estradiol and bisphenol A: involvement of the estrogen receptor and protein kinase C. | 2003 Sep 30 |
|
BMP7/ActRIIB regulates estrogen-dependent apoptosis: new biomarkers for environmental estrogens. | 2004 |
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Effects of the pesticides prochloraz and methiocarb on human estrogen receptor alpha and beta mRNA levels analyzed by on-line RT-PCR. | 2004 Aug |
|
Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone. | 2004 Dec 1 |
|
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 |
|
17beta-estradiol antagonizes cardiomyocyte hypertrophy by autocrine/paracrine stimulation of a guanylyl cyclase A receptor-cyclic guanosine monophosphate-dependent protein kinase pathway. | 2004 Jan 20 |
|
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 |
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Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials. | 2004 Mar |
|
Resveratrol modulates the phosphoinositide 3-kinase pathway through an estrogen receptor alpha-dependent mechanism: relevance in cell proliferation. | 2004 Mar 20 |
|
Small nuclear RING finger protein expression during gonad development: regulation by gonadotropins and estrogen in the postnatal ovary. | 2004 May |
|
Xenoestrogen-induced ERK-1 and ERK-2 activation via multiple membrane-initiated signaling pathways. | 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 |
|
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 |
|
Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor beta induces proliferation of endometrial stromal cells. | 2005 Dec |
|
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 |
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Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. | 2005 Jul 15 |
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Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens. | 2005 Jul-Aug |
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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 |
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CSN5/Jab1 is involved in ligand-dependent degradation of estrogen receptor {alpha} by the proteasome. | 2005 Jun |
|
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 increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. | 2005 Oct |
|
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 |
|
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
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/fulvestrant.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24793639
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.
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Classification Tree | Code System | Code | ||
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WHO-VATC |
QL02BA03
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LIVERTOX |
NBK548072
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NDF-RT |
N0000175582
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NCI_THESAURUS |
C2116
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NDF-RT |
N0000000168
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WHO-ATC |
L02BA03
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NDF-RT |
N0000175826
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EMA ASSESSMENT REPORTS |
FASLODEX (AUTHORIZED: BREAST NEOPLASMS)
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7658
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N0000000145
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PRIMARY | Estrogen Receptor Antagonists [MoA] | ||
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1255
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DB00947
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22X328QOC4
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282357
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759879
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C1379
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22X328QOC4
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100000089504
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7712
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KK-128
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31638
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129453-61-8
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SUB13933MIG
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FULVESTRANT
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104741
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1286650
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1015
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m5583
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CHEMBL1358
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DTXSID4022369
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C070081
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE LESS ACTIVE (PARENT)
PARENT (METABOLITE ACTIVE)