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Fulvestrant

Indications and Usage Mechanisms of Action Pharmacokinetics Adverse reactions
Fulvestrant
Fulvestrant structure
CAS No.
129453-61-8
Chemical Name:
Fulvestrant
Synonyms
139028;CS-670;ZD 9238;FASLODEX;zd182780;zm182780;Fulvtrant;Fulvestran;ICH-182780;ICI-187280
CBNumber:
CB0698542
Molecular Formula:
C32H47F5O3S
Formula Weight:
606.77
MOL File:
129453-61-8.mol

Fulvestrant Properties

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
form 
powder
pka
10.27±0.70(Predicted)
InChIKey
VWUXBMIQPBEWFH-WCCTWKNTSA-N
CAS DataBase Reference
129453-61-8(CAS DataBase Reference)
FDA UNII
22X328QOC4
NCI Dictionary of Cancer Terms
Faslodex; fulvestrant; ICI 182780
NCI Drug Dictionary
Faslodex
ATC code
L02BA03
SAFETY
  • Risk and Safety Statements
WGK Germany  3
RTECS  KG7623000
HS Code  2937230000

Fulvestrant price More Price(43)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 5.31042 Estrogen Receptor Antagonist, ICI 182,780 - CAS 129453-61-8 - Calbiochem 129453-61-8 10 mg $206 2021-12-16 Buy
Sigma-Aldrich I4409 Fulvestrant >98% (HPLC) 129453-61-8 25mg $155 2021-12-16 Buy
Sigma-Aldrich Y0001399 Fulvestrant European Pharmacopoeia (EP) Reference Standard 129453-61-8 $190 2021-12-16 Buy
Sigma-Aldrich Y0001413 Fulvestrant for system suitability European Pharmacopoeia (EP) Reference Standard 129453-61-8 $190 2021-12-16 Buy
Sigma-Aldrich 1286650 Fulvestrant United States Pharmacopeia (USP) Reference Standard 129453-61-8 200mg $922 2021-12-16 Buy

Fulvestrant Chemical Properties,Uses,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.

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.

Chemical 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 7α- and 7β-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.

Fulvestrant synthesis

153004-31-0
129453-61-8
Synthesis of Fulvestrant from (7a,17b)-7-[9-[(4,4,5,5,5-Pentafluoropentyl)thio]nonyl]-estra-1,3,5(10)-triene-3,17-diol

Fulvestrant Preparation Products And Raw materials

Raw materials

Preparation Products


Fulvestrant Suppliers

Global( 370)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Lianyungang happen teng technology co., LTD
15950718863
wang666xt@163.com CHINA 296 58
TianYuan Pharmaceutical CO.,LTD
+86-755-23284190 13684996853
+86-755-23284190 sales@tianpharm.com CHINA 305 58
Xi'an Yutbon Pharmaceutical Technology Co., Ltd
+8618717328141 +86-029-81140587
086-029-84536389 sales@yutbon.com China 412 58
Echemi Group
18905328650 86-18905328650
pharma@echemi.com CHINA 215 58
AFINE CHEMICALS LIMITED
008657185134551
008657185134895 info@afinechem.com CHINA 15559 58
Capot Chemical Co.,Ltd.
+86(0)13336195806 +86-571-85586718
+86-571-85864795 sales@capotchem.com China 20012 60
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com China 22607 55
Hangzhou FandaChem Co.,Ltd.
008615858145714
+86-571-56059825 fandachem@gmail.com CHINA 9134 55
Guangzhou PI PI Biotech Inc
+8618371201331
020-81716319 sales@pipitech.com;87478684@qq.com China 3283 55
Shanghai Yingrui Biopharma Co., Ltd.
+86-21-33585366 E-mail:sales03@shyrchem.com
+86-21-34979012 sales03@shyrchem.com CHINA 739 60

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View Lastest Price from Fulvestrant manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2022-01-22 Fulvestrant
129453-61-8
US $0.00 / KG 100g 98%+ 100kg WUHAN CIRCLE POWDER TECHNOLOGY CO.,LTD
2021-11-30 Fulvestrant
129453-61-8
US $795.00 / g/Bag 1g 99% 1kg Baoji Guokang Bio-Technology Co., Ltd.
2021-10-20 Fulvestrant
129453-61-8
US $350.00 / KG 1KG 99% 9000kg/per week Hebei Lingding Biological Technology Co., Ltd

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