풀 베스트 한 C화학적 특성, 용도, 생산
개요
많은 유방암에는 에스트로겐 수용체가 있으며이 종양의 성장은 에스트로겐에 의해 자극 될 수 있습니다. Fulvestrant는 에스트로겐 수용체 다운 레귤레이터이며, 이는 에스트로겐 수용체가 신체의 에스트로겐과 경쟁하여 에스트로겐 수용체 사이트에 결합 함을 의미합니다. 일단 그것이 사이트에 결합하면 수용체가 파괴되어 에스트로겐에 대한 정상적인 세포 반응을 예방합니다.
용도
풀 베스트 한 파우더 합성 에스트로겐 수용체 길항제입니다. 풀 옥시 겐은 유방암 세포에서 에스트로겐 수용체와 경쟁적으로 결합하여 에스트로겐 수용체가 변형되고 에스트로겐 결합이 감소합니다. (부분 작용제 효과가있는) 타목시펜과 아로마 타제 억제제 (종양 세포에 유효한 에스트로겐을 감소 시킴)와는 다릅니다.
개요
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.
화학적 성질
White or almost white powder.
용도
A novel steroidal estrogen antagonist reported to lack any partial agonist activity. Antineoplastic (hormonal).
정의
ChEBI: A 3-hydroxy steroid that is 17beta-estradiol in which the 7alpha hydrogen has been replaced by a nonyl group in which one of the hydrogens of the terminal methyl has been replaced by a (4,4,5,5,5-pentafluoropentyl)sulfinyl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.
일반 설명
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 ER
αand ER
βandan 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.
생물학적 활성
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.
부작용
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.
풀 베스트 한 준비 용품 및 원자재
원자재
4,4,5,5,5-Pentafluoro-1-pentanol
(7a,17b)-7-[9-[(4,4,5,5,5-Pentafluoropentyl)thio]nonyl]-estra-1,3,5(10)-triene-3,17-diol
(7alpha,17beta)-17-(Acetyloxy)-7-(9-bromononyl)estr-4-en-3-one
3-O-Methyl Fulvestrant
(7a,17b)-7-7-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]-estra-1,3,5(10)-triene-3,17-diol 17-acetate
Estra-1,3,5(10)-triene-3,17-diol,7-[9-[(4,4,5,5,5-pentafluoropentyl)thio]nonyl]-,17-acetate,(7a,17b)-
데하이드로난드롤론
메탄술폰산4,4,5,5,5-펜타플루오로-펜틸에스테르
난드롤론
준비 용품
