(1S,9R,10R,11S,14S,15S)-15-methyl-9-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]tetracyclo[8.7.0.02,7.011,15]heptadeca-2,4,6-triene-5,14-diol

• ChemBase编号: 823
• 分子式: C32H47F5O3S
• 平均质量: 606.770796
• 单一同位素质量: 606.31660746
• SMILES: S(=O)(CCCCCCCCC[C@H]1[C@H]2[C@H]3[C@](CC[C@@H]2c2c(C1)cc(O)cc2)([C@@H](O)CC3)C)CCCC(F)(F)C(F)(F)F
• Canonical SMILES: O=S(CCCC(C(F)(F)F)(F)F)CCCCCCCCC[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1CC[C@@H]([C@]1(CC2)C)O
• InChI: 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
• InChIKey: VWUXBMIQPBEWFH-WCCTWKNTSA-N

名称和登记号

名称

• IUPAC标准名: (1S,9R,10R,11S,14S,15S)-15-methyl-9-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]tetracyclo[8.7.0.0^2,^7.0^1^1,^1^5]heptadeca-2,4,6-triene-5,14-diol; (1S,9R,10R,11S,14S,15S)-15-methyl-9-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5,14-diol; (1S,9R,10R,11S,14S,15S)-15-methyl-9-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2,4,6-triene-5,14-diol
• IUPAC传统名: fulvestrant; (1S,9R,10R,11S,14S,15S)-15-methyl-9-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5,14-diol; (1S,9R,10R,11S,14S,15S)-15-methyl-9-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2,4,6-triene-5,14-diol
• 商标名: Faslodex
• 别名: (7a,17b)-7-[9-[(4,4,5,5,5pentafluoropentyl)Sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol; ZD 182780; ZD 9238; ZM 182780; Fulvestrant; (7α,17β)-7-[9-[4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol; ICI 182,780; fulvestrant; Fulvestrant; Faslodex; ICI 182780

登记号

• CAS号: 129453-61-8
• MDL号: MFCD00903953
• PubChem SID: 160964286
• PubChem CID: 104741

理论计算性质

JChem

• Acid pKa: 10.320843
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): 7.571834
• LogD (pH = 7.4): 7.571323
• Log P: 7.571841
• 摩尔折射率: 155.337 cm^3
• 极化性: 59.35865 Å^3
• 极化表面积: 57.53 Å^2
• 可自由旋转的化学键: 15
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 6.54
• LOG S: -4.96
• 溶解度: 6.72e-03 g/l

分子性质

理化性质

• 溶解度: Chloroform; DMSO; DMSO: >5 mg/mL
• 外观: powder; White Solid
• 熔点: 104-106°C
• 疏水性(logP): 8.9

安全信息

• 保存条件: -20°C; -20°C Freezer
• RTECS编号: KG7623000
• 德国WGK号: 3
• 个人保护装置: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• 保存温度: 2-8°C

药理学性质

• 作用靶点: estrogen receptor

产品相关信息

• 纯度: >98% (HPLC)
• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C32H47F5O3S

详细说明

DrugBank - DB00947

• Drug Groups: approved; investigational
• 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.
• Indication: For the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy.
• Pharmacology: Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist effects.
• Toxicity: There is no clinical experience with overdosage in humans.
• Affected Organisms: Humans and other mammals
• Biotransformation: Metabolism of fulvestrant appears to involve combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids, including oxidation, aromatic hydroxylation, conjugation with glucuronic acid and/or sulphate at the 2, 3 and 17 positions of the steroid nucleus, and oxidation of the side chain sulphoxide. Identified metabolites are either less active or exhibit similar activity to fulvestrant in antiestrogen models. Studies using human liver preparations and recombinant human enzymes indicate that cytochrome P-450 3A4 (CYP 3A4) is the only P-450 isoenzyme involved in the oxidation of fulvestrant; however, the relative contribution of P-450 and non-P-450 routes in vivo is unknown.
• Half Life: 40 days
• Protein Binding: 99% (mainly VLDL, LDL, and HDL)
• Elimination: Fulvestrant was rapidly cleared by the hepatobiliary route with excretion primarily via the feces (approximately 90%).; Renal elimination was negligible (less than 1%).
• Distribution: * 3 to 5 L/kg
• References: Kansra S, Yamagata S, Sneade L, Foster L, Ben-Jonathan N: Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Mol Cell Endocrinol. 2005 Jul 15;239(1-2):27-36. [Pubmed] ; Kabos P, Borges VF: Fulvestrant: a unique antiendocrine agent for estrogen-sensitive breast cancer. Expert Opin Pharmacother. 2010 Apr;11(5):807-16. [Pubmed] ; Bross PF, Cohen MH, Williams GA, Pazdur R: FDA drug approval summaries: fulvestrant. Oncologist. 2002;7(6):477-80. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1191

Research Area: Breast cancer
Biological Activity:
Fulvestrant (Faslodex) is a synthetic estrogen receptor antagonist or selective estrogen receptor down-regulator (SERD). Unlike tamoxifen (which has partial agonist effects) and the aromatase inhibitors (which reduce the estrogen available to tumor cells), fulvestrant binds competitively to estrogen receptors in breast cancer cells, resulting in estrogen receptor deformation and decreased estrogen binding. In vitro studies indicate that fulvestrant reversibly inhibits the growth of tamoxifen-resistant, estrogen-sensitive, human breast cancer cell lines. [1] Fulvestrant is used for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. [2]

Sigma Aldrich - I4409

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.

Toronto Research Chemicals - F862500

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

参考文献

• Kansra S, Yamagata S, Sneade L, Foster L, Ben-Jonathan N: Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Mol Cell Endocrinol. 2005 Jul 15;239(1-2):27-36. Pubmed
• Kabos P, Borges VF: Fulvestrant: a unique antiendocrine agent for estrogen-sensitive breast cancer. Expert Opin Pharmacother. 2010 Apr;11(5):807-16. Pubmed
• Bross PF, Cohen MH, Williams GA, Pazdur R: FDA drug approval summaries: fulvestrant. Oncologist. 2002;7(6):477-80. Pubmed
• http://en.wikipedia.org/wiki/Fulvestrant
• Wakeling, A.E., et al.: Cancer Res., 51, 3867 (1991)
• Howell, A., et al.: Br. J. Cancer, 74, 300 (1991)
• Robertson, J.F., et al.: Cancer Res., 61, 6739 (1991)