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

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	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

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	Antagonist 2,778		0.0631 nM [IC50]
MCF7 21	Inhibitor 8,297		0.1 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hormone receptor positive metastatic breast cancer 3	Primary		Approved 8,429	FASLODEX

C_max

Value	Dose	Co-administered	Analyte	Population
25.1 ng/mL	500 mg single, intramuscular		FULVESTRANT plasma	Homo sapiens
11.4 ng/mL	250 mg single, intramuscular		FULVESTRANT plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
11400 ng × h/mL	500 mg single, intramuscular		FULVESTRANT plasma	Homo sapiens
176 ng × day/mL	250 mg single, intramuscular		FULVESTRANT plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
40 day	250 mg single, intramuscular		FULVESTRANT plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1%	250 mg single, intramuscular		FULVESTRANT plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
500 mg 1 times / month multiple, intramuscular Highest studied dose	unhealthy, 54 years
500 mg 1 times / month multiple, intramuscular	unhealthy, 56 years	Disc. AE: Epidermal necrolysis...

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AEs

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AE	Significance	Dose	Population
Epidermal necrolysis	1 patient Disc. AE	500 mg 1 times / month multiple, intramuscular	unhealthy, 56 years

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inhibitor 1,587 inducer 781	inhibitor 1,767 inducer 389	inhibitor 1,852 inducer 97

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2C19 1,478	UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A8 283	CYP1A2 701 CYP2C19 293

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 1,692	inducer 1,573	no
CYP1A2 1,692	inhibitor 3,277	no
CYP2C19 1,553	inducer 1,573	no
CYP2C19 1,553	inhibitor 3,277	no
CYP2C9 1,819	inducer 1,573	no

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Drug as victim

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Target	Modality	Activity	Clinical evidence
UGT1A1 418	substrate 3,367	yes
UGT1A3 422	substrate 3,367	yes
UGT1A4 347	substrate 3,367	yes
UGT1A8 283	substrate 3,367	yes
CYP3A4 1,737	substrate 3,367	yes	no (co-administration study)

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Sourcing

Sourcing

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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
eMolecules	6719147	https://www.emolecules.com/cgi-bin/more?vid=6719147
Selleck Chemicals	Fulvestrant	http://www.selleckchem.com/products/Fulvestrant.html

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PubMed

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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
Estrogen directly respresses gonadotropin-releasing hormone (GnRH) gene expression in estrogen receptor-alpha (ERalpha)- and ERbeta-expressing GT1-7 GnRH neurons.	1999 Nov	10537130
The aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT) heterodimer interacts with naturally occurring estrogen response elements.	1999 Nov 25	10619402

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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
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

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Classification Tree

Code System

Code

Anti-estrogens

WHO-VATC

QL02BA03

Breast Cancer

LIVERTOX

NBK548072

Established Pharmacologic Class

NDF-RT

N0000175582

Antiestrogen

NCI_THESAURUS

C2116

Steroid Receptor Modulators

NDF-RT

N0000000168

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Code System

Code

Type

Description

HSDB

7658

PRIMARY

NDF-RT

N0000000145

PRIMARY

Estrogen Receptor Antagonists [MoA]

DRUG CENTRAL

1255

PRIMARY

DRUG BANK

DB00947

PRIMARY

FDA UNII

22X328QOC4

PRIMARY

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Related Record

Type

Details


					22X328QOC4

FULVESTRANT

BASIS OF STRENGTH->SUBSTANCE

Interaction Type:

ASSAY (HPLC)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [97 to 102] WEIGHT PERCENT (limits)


					22X328QOC4

FULVESTRANT

BASIS OF STRENGTH->SUBSTANCE

Interaction Type:

ASSAY (HPLC)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [97 to 102] WEIGHT PERCENT (limits)


					SIDP85PFD6

ESTROGEN RECEPTOR

TARGET -> INHIBITOR

Qualification:

IC50

Amount:

24 (average)


					SIDP85PFD6

ESTROGEN RECEPTOR

TARGET -> INHIBITOR

Comments:

Selective estrogen receptor degrader (SERD)

Interaction Type:

BINDING

Qualification:

IC50

Amount:

1.2 NANOMOLAR (average)
ER.ALPHA. DEGRADATION


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

99 % (average)

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Related Record

Type

Details


					RB33MP5RCR

FULVESTRANT 3-.BETA.-D-GLUCURONIDE

METABOLITE -> PARENT

Amount:


					55928538EN

FULVESTRANT SULFONE

METABOLITE -> PARENT

Amount:


					WJ34L4WA5M

FULVESTRANT 3-SULFATE

METABOLITE -> PARENT

Amount:


					4U9ZQ7YHR9

FULVESTRANT 17-KETONE

METABOLITE LESS ACTIVE -> PARENT

Amount:


					D9J6E34HZC

FULVESTRANT 17-.BETA.-D-GLUCURONIDE

METABOLITE -> PARENT

Amount:

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Related Record

Type

Details


					52A05VPF7S

.DELTA.6,7-FULVESTRANT

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [<0.1] WEIGHT PERCENT (limits)


					OMU8ZM6O3U

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

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [<0.3] PERCENT PEAK AREA (limits)


					98WY072U8M

7-(9-((4,4,5,5,5-PENTAFLUOROPENTYL)SULFINYL)NONYL)-3,17.BETA.-DIHYDROXYESTRA-1,3,5(10)-TRIEN-6-ONE

IMPURITY -> PARENT

Comments:

For the calculation of contents, multiply the peak areas by 0.3

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [<0.15] PERCENT PEAK AREA (CORRECTION FACTOR) (limits)


					55928538EN

FULVESTRANT SULFONE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [<0.2] WEIGHT PERCENT (limits)


					M1IH3Z2RR8

6-KETO-FULVESTRANT

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [<0.1] WEIGHT PERCENT (limits)

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Related Record

Type

Details


					22X328QOC4

FULVESTRANT

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount
Biological Half-life	PHARMACOKINETIC	40 days (average)

Volume of Distribution	PHARMACOKINETIC	[3 to 5] Liters/Kilogram (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator