(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 ID: 823
• Molecular Formular: C32H47F5O3S
• Molecular Mass: 606.770796
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: (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 Traditional name: 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
• Brand Name: Faslodex
• Synonyms: (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

Database IDs

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

CALCULATED PROPERTIES

JChem

• Acid pKa: 10.320843
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 7.571834
• LogD (pH = 7.4): 7.571323
• Log P: 7.571841
• Molar Refractivity: 155.337 cm^3
• Polarizability: 59.35865 Å^3
• Polar Surface Area: 57.53 Å^2
• Rotatable Bonds: 15
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 6.54
• LOG S: -4.96
• Solubility (Water): 6.72e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO; DMSO: >5 mg/mL
• Apperance: powder; White Solid
• Melting Point: 104-106°C
• Hydrophobicity(logP): 8.9

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: KG7623000
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: estrogen receptor

Product Information

• Purity: >98% (HPLC)
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C32H47F5O3S

DETAILS

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).

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
• 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)