Indications and Usage Mechanisms of Action Pharmacokinetics Adverse reactions
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Fulvestrant

Indications and Usage Mechanisms of Action Pharmacokinetics Adverse reactions
Product Name
Fulvestrant
CAS No.
129453-61-8
Chemical Name
Fulvestrant
Synonyms
Astrazeneca;FASLODEX;ICI 182,780;Fulvestrant CRS;139028;CS-670;ZD 9238;zd182780;zm182780;Fulvtrant
CBNumber
CB0698542
Molecular Formula
C32H47F5O3S
Formula Weight
606.77
MOL File
129453-61-8.mol
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Fulvestrant Property

Melting point:
104-106°C
Boiling point:
674.8±55.0 °C(Predicted)
Density 
1.201±0.06 g/cm3(Predicted)
storage temp. 
2-8°C
solubility 
DMSO: >5mg/mL
pka
10.27±0.70(Predicted)
form 
powder
color 
White
Stability:
Stable for 2 years as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
InChIKey
VWUXBMIQPBEWFH-WCCTWKNTSA-N
SMILES
[C@@]12([H])[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC3C=C(O)C=CC=3[C@@]1([H])CC[C@]1(C)[C@H](CC[C@@]21[H])O |&1:0,2,32,36,38,41,r|
CAS DataBase Reference
129453-61-8(CAS DataBase Reference)
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Safety

WGK Germany 
3
RTECS 
KG7623000
HS Code 
2937230000
Hazardous Substances Data
129453-61-8(Hazardous Substances Data)
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Danger
Hazard statements

H413May cause long lasting harmful effects to aquatic life

Precautionary statements

P273Avoid release to the environment.

P501Dispose of contents/container to..…

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
I4409
Product name
Fulvestrant
Purity
>98% (HPLC)
Packaging
25mg
Price
$187
Updated
2024/03/01
Sigma-Aldrich
Product number
5.31042
Product name
Estrogen Receptor Antagonist, ICI 182,780 - CAS 129453-61-8 - Calbiochem
Packaging
10mg
Price
$246
Updated
2024/03/01
Sigma-Aldrich
Product number
1286650
Product name
Fulvestrant
Purity
United States Pharmacopeia (USP) Reference Standard
Packaging
200mg
Price
$1160
Updated
2024/03/01
Cayman Chemical
Product number
10011269
Product name
Fulvestrant
Purity
≥98%
Packaging
1mg
Price
$32
Updated
2024/03/01
Cayman Chemical
Product number
10011269
Product name
Fulvestrant
Purity
≥98%
Packaging
5mg
Price
$86
Updated
2024/03/01
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Fulvestrant Chemical Properties,Usage,Production

Indications and Usage

Fulvestrant is a muscle injection drug developed by the company AstraZeneca and is suitable for treating postmenopausal women with estrogen receptor-positive metastasized breast cancer whose condition continued to worsen despite antiestrogen treatment. Fulvestrant is the only antiestrogen drug that can be widely clinically used following unsuccessful tamoxifen treatment. This drug is a type of endocrine therapy, so it will not cause any adverse effects commonly seen in chemotherapy, giving it relatively good patient compliance. Multiple clinical trials have found that 250mg Fulvestrant is effective and consistently safe as a second line of treatment for advanced breast cancer.

Mechanisms of Action

Many breast cancer cells contain estrogen receptors (ER), so estrogen stimulates breast cancer growth. Fulvestrant is a steroid estrogen receptor antagonist, and its chemical structure is similar to estradiol, except that its 7α position contains a linking group. Fulvestrant is a 17β-estradiol alkylamine analogue, and it binds with, prevents, and decreases ER to inhibit the estrogen signal transduction pathway. It binds competitively with ER, has a similar affinity with ER as estrogen, and inhibits gene activation stimulated by estrogen, thus affecting necessary estrogen-related processes in cell circulation. Its fulvastans have a similar affinity with ER as estrogen and is 100 times that of tamoxifen.

Pharmacokinetics

Fulvestrant has a relatively poor oral bioavailability, so it is commonly injected into the muscle with lipids as excipients. In an open, random and multicenter study on postmenopausal women with advanced breast cancer, one 5ml or 2 2.5ml dosages containing 250mg were injected, and their pharmacokinetics and poisonous side effects did not differ greatly, while its blood concentration was dose-dependent and had individual differences. In the 7-day treatment period, serum LH, FSH or SBHG levels did not change significantly. This drug does not pass through the blood-brain barrier and will not cause side effects such as vasomotor symptoms.

Adverse reactions

Fulvestrant causes relatively fewer side effects, including brief vaginal bleeding, body odor change, and sleepwalking. There have not been any reports of effects such as vaginal dryness, weight gain, blood clotting abnormalities, thrombus formation and libido change, and characteristics such as facial flushing and sweating are not affected. A small-scale stage III clinical trial on 19 women with metastasized breast cancer who used this drug showed that its clinical efficacy was 67% and there were no serious safety issues. It showed that continuous monthly injections were crucial and that it was well-tolerated, with only slight swelling and paint at injection site, while facial flushing, uterine lining thickness, sex hormone binding globulin levels, follicle stimulating hormones levels, and luteinizing hormone levels all showed no change.

Description

Fulvestrant was launched in the US as a novel once monthly injectable steroidal estrogen antagonist for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following estrogen therapy. This 7a-alkylsulphinyl derivative of estradiol can be prepared in 10 steps from 6,7- didehydro-19-nor-testosterone by successive conjugate addition of the organocuprate derived from O-protected 9-bromononan-l-o1 followed by aromatization of the resulting enone, then activation of the protected primary alcohol, substitution with 4,4,5,5,5- pentafluoropentanthiol and oxidation to the sulfoxide. Fulvestrant is the first “pure” estrogen antagonist from a novel class known as selective estrogen receptor down regulators (SERDs). It binds to the estrogen receptor (ER), with affinity close to that of estradiol and 100 fold greater than that of tamoxifen (a partial estrogen antagonist), preventing estrogen-stimulated gene activation, thereby interfering with the estrogenrelated processes essential for cell-cycle completion. Fulvestrant also appears to downregulate the ER by 80-90% often to non detectable level both in vitro and in vivo. In comparison to tamoxifen, fulvestrant is devoid of systemic estrogenic activity, it displays no uterotrophic activity and is able to block the uterine stimulation of estradiol or tamoxifen. Furthermore, fulvestrant completely blocks the cell growth in tamoxifen-resistant breast cancer cell-lines and prevents growth of tamoxifen resistant tumor in mice. In clinical trials, it was also shown that fulvestrant is comparable to anastrozole (a third generation aromatase inhibitor) both in efficacy and tolerability in postmenopausal women with tamoxifen-resistant advanced breast cancers.

Chemical Properties

White or almost white powder.

Originator

Astra Zeneca (UK)

Uses

A novel steroidal estrogen antagonist reported to lack any partial agonist activity. Antineoplastic (hormonal).

Uses

antiestrogen

Definition

ChEBI: A 3-hydroxy steroid that is 17beta-estradiol in which the 7alpha hydrogen has been replaced by a nonyl group in which one of the hydrogens of the terminal methyl has been replaced by a (4,4,5,5,5-pentafluoropentyl)sulfinyl group. An estrogen receptor antagonist, it is used in the treatment of breast cancer.

brand name

Faslodex (AstraZeneca).

General Description

Fulvestrant, 7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17β-diol (Faslodex), is an antagonist structurally based onthe estradiol structure, with a long, substituted alkyl chainattached at the 7α-position of the steroid skeleton. Whenbound to the ERs, this alkyl chain induces a conformationof the receptor distinctive from that formed upon estradiolor tamoxifen binding, preventing agonist action.Fulvestrant is a pure antagonist at both ERαand ERβandan ER downregulator (stimulates degradation of the ER),completely lacking the agonist activity that is seen with tamoxifenor raloxifene. The different pharmacological profileof fulvestrant allows the use of this agent in womenwho have had disease progression after prior antiestrogentherapy (typically tamoxifen), providing an alternative toaromatase inhibitors.

Biological Activity

A high affinity estrogen receptor antagonist (IC 50 = 0.29 nM), devoid of any partial agonism both in vitro and in vivo . Also high affinity agonist at the membrane estrogen receptor GPR30.

Biochem/physiol Actions

Fulvestrant (ICI 182,780) is a selective estrogen receptor down-regulator (SERD). Fulvestrant is a high affinity estrogen receptor antagonist. IC50 = 0.29 nM. Fulvestrant is the first "pure" antiestrogen with no agonistic activity both in vitro and in vivo.

Clinical Use

Treatment of postmenopausal women with oestrogenreceptor- positive, locally advanced or metastatic breast cancer

Side effects

Side effects appear to be minimal and include several GI symptoms , headache, and hot flashes . There is no clinical evidence of uterine stimulation or laboratory evidence of stimulation of endometrial carcinoma models. Fulvestrant should not be adm inistered to women who are pregnant, who are taking antic oagulants, or who have thrombocytopenia.

Synthesis

Fulvestrant is administered as a once a month i. m. injection. Several routes for the synthesis of fulvestrant (12) were published. One of the best routes is depicted in the scheme. The conjugate addition of Grignard reagent derived from bromide 130 with dienone 129 gave adduct 131 as a mixture of 7|á- and 7|?-isomers in a ratio of 2.5:1 in 90-95% yield. Aromatization of the A-ring with copper bromide/lithium bromide in acetic acid followed by hydrolysis of the ester group provided diol 132 in 80-85% yield. Oxidation of the side chain from sulfite to sulfone followed by crystallization provided fulvestrant (12) in 30% overall yield from dienone 129.

Metabolism

The metabolism of fulvestrant has not been fully evaluated, but involves combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids. Identified metabolites (includes 17-ketone, sulphone, 3-sulphate, 3- and 17-glucuronide metabolites) are either less active or exhibit similar activity to fulvestrant in anti-oestrogen models.
Fulvestrant is eliminated mainly in metabolised form. The major route of excretion is via the faeces.

storage

Room temperature

References

Osborne et al. (2004), Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action; Br. J. Cancer 90 (Suppl 1):S2 Thomas et al. (2005), Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells; Endocrinology 146 624 Wardley (2002), Fulvestrant: a review of its development, pre-clinical and clinical data; Int. J. Clin. Pract. ?56 305 Castro et al. (2012),?Coumestrol has neuroprotective effects before and after cerebral ischemia in female rats; Brain Res.?1474 82 Blackburn et al. (2018),?Fulvestrant for the treatment of advanced breast cancer; Expert Rev. Anticancer Ther. 18 619

Fulvestrant Preparation Products And Raw materials

Raw materials

Preparation Products

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Fulvestrant Suppliers

Hubei huizepu Pharmaceutical Technology Co., Ltd
Tel
0185-0185-07139096 18507139096
Fax
QQ:1925957016
Email
18507139096@163.com
Country
China
ProdList
3855
Advantage
58
Hangzhou Lenny Technology Co. , Ltd.
Tel
571-88086013
Fax
0571- 88088387
Email
sunnie@rdpharm.com
Country
China
ProdList
88
Advantage
60
Chongqing Genco Pharmaceutical Co.,Ltd
Tel
023-88654579 13637703915
Fax
375097861
Email
375097861@qq.com
Country
China
ProdList
297
Advantage
58
Shanghai tingchong biology science and technology co., ltd
Tel
18964309092 18964309092
Email
2769493375@qq.com
Country
China
ProdList
2634
Advantage
58
Jinan Hongkangda Chemical Co., Ltd
Tel
0531-88901705 18753193522
Email
810353473@qq.com
Country
China
ProdList
137
Advantage
58
Jiaxing Hengrui Biotechnology Co. LTD
Tel
0573-82672231 13757365595
Fax
QQ:715584339
Email
regen_chemical1@163.com
Country
China
ProdList
3844
Advantage
58
Hangzhou nuotong biotechnology co. LTD
Tel
86-571-88589737 15268405618
Email
info@sinopep.com
Country
China
ProdList
87
Advantage
58
Shaoxing Fangxiao Chemical Co., LTD
Tel
13456999252
Email
shellyhouse39@126.com
Country
China
ProdList
49
Advantage
58
ChemStrong Scientific Co.,Ltd
Tel
0755-66853366 15920483169
Fax
0755-28363542
Email
sales@chem-strong.com
Country
China
ProdList
17944
Advantage
56
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2923
Advantage
55
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View Lastest Price from Fulvestrant manufacturers

hebei hongtan Biotechnology Co., Ltd
Product
Fulvestrant 129453-61-8
Price
US $30.00/kg
Min. Order
1kg
Purity
98%
Supply Ability
2000kg
Release date
2024-03-21
WUHAN CIRCLE POWDER TECHNOLOGY CO.,LTD
Product
Fulvestrant 129453-61-8
Price
US $0.00/KG
Min. Order
100g
Purity
98%+
Supply Ability
100kg
Release date
2020-11-04
shandong perfect biotechnology co.ltd
Product
Fulvestrant 129453-61-8
Price
US $0.00/KG
Min. Order
1KG
Purity
98% HPLC
Supply Ability
500kgs
Release date
2023-07-07

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