(1S,2R,10R,11S,15S)-2,15-dimethyl-8-methylidenetetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-diene-5,14-dione

• ChemBase编号: 864
• 分子式: C20H24O2
• 平均质量: 296.40336
• 单一同位素质量: 296.17763001
• SMILES: O=C1[C@@]2([C@H]([C@H]3[C@H](CC2)[C@@]2(C(=CC(=O)C=C2)C(=C)C3)C)CC1)C
• Canonical SMILES: O=C1C=C[C@]2(C(=C1)C(=C)C[C@@H]1[C@@H]2CC[C@]2([C@H]1CCC2=O)C)C
• InChI: InChI=1S/C20H24O2/c1-12-10-14-15-4-5-18(22)20(15,3)9-7-16(14)19(2)8-6-13(21)11-17(12)19/h6,8,11,14-16H,1,4-5,7,9-10H2,2-3H3/t14-,15-,16-,19+,20-/m0/s1
• InChIKey: BFYIZQONLCFLEV-DAELLWKTSA-N

名称和登记号

名称

• IUPAC标准名: (1S,2R,10R,11S,15S)-2,15-dimethyl-8-methylidenetetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-diene-5,14-dione; (1S,2R,10R,11S,15S)-2,15-dimethyl-8-methylidenetetracyclo[8.7.0.0^2,^7.0^1^1,^1^5]heptadeca-3,6-diene-5,14-dione
• IUPAC传统名: exemestane
• 商标名: Aromasin; Exemestance
• 别名: FCE-24304; 6-Methylene-androsta-1,4-diene-3,17-dione; Exemestano [INN-Spanish]; Exemestanum [INN-Latin]; exemestane; Exemestane; Aromasin; 6-Methyleneandrosta-1,4-diene-3,17-dione; Exemestane

登记号

• CAS号: 107868-30-4
• MDL号: MFCD00866994
• PubChem SID: 160964327; 46508243
• PubChem CID: 60198

理论计算性质

JChem

• Acid pKa: 19.957294
• 质子受体: 2
• 质子供体: 0
• LogD (pH = 5.5): 3.8661478
• LogD (pH = 7.4): 3.8661478
• Log P: 3.8661478
• 摩尔折射率: 89.0269 cm^3
• 极化性: 34.07716 Å^3
• 极化表面积: 34.14 Å^2
• 可自由旋转的化学键: 0
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.67
• LOG S: -4.64
• 溶解度: 6.83e-03 g/l

分子性质

理化性质

• 溶解度: Acetonitrile; Chloroform; DMSO; DMSO: ≥20 mg/mL; Non-soluble
• 外观: Off-White Solid; white to off-white powder
• 熔点: 191-193°C
• 比旋光度: [α]/D +250 to +300°, c = 1 in methanol
• 疏水性(logP): 3.7

安全信息

• 保存条件: -20°C; -20°C Freezer
• 欧盟危险性物质标志: 环境危害性(Nature polluting) (N); 有毒(Toxic) (T)
• 德国WGK号: 3
• 危险公开号: 60-61-51
• 安全公开号: 53-22-36/37-57
• GHS危险品标识: GHS07; GHS08
• GHS警示词: Danger
• GHS危险声明: H319-H360
• GHS警示性声明: P201-P305 + P351 + P338-P308 + P313
• 保存温度: room temp

药理学性质

• 作用靶点: aromatase enzyme

产品相关信息

• 纯度: ≥98% (HPLC); 96%; 98%
• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C20H24O2

详细说明

DrugBank - DB00990

• Drug Groups: approved; investigational
• Description: Exemestane is an oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation.
• Indication: For the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
• Pharmacology: Aromatase is an enzyme that converts hormones to estrogen in the body's adrenal glands. The aromatase inhibitors (AIs) are drugs that reduce estrogen levels by blocking the action of aromatase in the adrenal glands. The selective AIs (SAIs) selectively reduce levels of estrogen without interfering with levels of other steroid hormones that are produced by the adrenal gland. Drugs in this class include anastrozole (Arimidex ™), letrozole (Femara ™) and exemestane (Aromasin ™).
• Toxicity: Convulsions
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: 42%
• Half Life: 24 hours
• Protein Binding: 90% (mainly α1-acid glycoprotein and albumin)
• References: Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM: Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. [Pubmed] ; Robinson A: A review of the use of exemestane in early breast cancer. Ther Clin Risk Manag. 2009 Feb;5(1):91-8. Epub 2009 Mar 26. [Pubmed] ; Untch M, Jackisch C: Exemestane in early breast cancer: a review. Ther Clin Risk Manag. 2008 Dec;4(6):1295-304. [Pubmed] ; Abrial C, Durando X, Mouret-Reynier MA, Thivat E, Bayet-Robert M, Nayl B, Dubray P, Pomel C, Chollet P, Penault-Llorca F: Role of neo-adjuvant hormonal therapy in the treatment of breast cancer: a review of clinical trials. Int J Gen Med. 2009 Jul 30;2:129-40. [Pubmed] ; Nabholtz JM: Long-term safety of aromatase inhibitors in the treatment of breast cancer. Ther Clin Risk Manag. 2008 Feb;4(1):189-204. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1196

Research Area: Endocrinology
Biological Activity:
Exemestane is an irreversible, oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive breast cancer in postmenopausal women. [1]Its structure was related to the natural substrate androstenedione and it acts as a false substrate for the aromatase enzyme, an effect also known as "suicide inhibition."[1]The estrogen suppression rate for exemestane varies from 85% for estradiol (E2) to 95% for estrone (E1). [1]Exemestane was found to inhibit human placental aromatase with IC50 of 42 nM. [2]References on Exemestane[] Biochimica et Biophysica Acta, 2002, 1587:326– 337

Sigma Aldrich - PZ0006

Legal Information
Sold for research purposes under agreement from Pfizer Inc.
Biochem/physiol Actions
Exemestane is a steroidal antiestrogen and irreversible aromatase inhibitor. Exemestane acts as a false substrate for the aromatase enzyme. Exemestane also prevents the conversion of androgens to estrogens and is used to treat estrogen-dependent breast cancer.

Toronto Research Chemicals - E957000

An antineoplastic (hormonal).

参考文献

• Robinson A: A review of the use of exemestane in early breast cancer. Ther Clin Risk Manag. 2009 Feb;5(1):91-8. Epub 2009 Mar 26. Pubmed
• Untch M, Jackisch C: Exemestane in early breast cancer: a review. Ther Clin Risk Manag. 2008 Dec;4(6):1295-304. Pubmed
• Abrial C, Durando X, Mouret-Reynier MA, Thivat E, Bayet-Robert M, Nayl B, Dubray P, Pomel C, Chollet P, Penault-Llorca F: Role of neo-adjuvant hormonal therapy in the treatment of breast cancer: a review of clinical trials. Int J Gen Med. 2009 Jul 30;2:129-40. Pubmed
• Nabholtz JM: Long-term safety of aromatase inhibitors in the treatment of breast cancer. Ther Clin Risk Manag. 2008 Feb;4(1):189-204. Pubmed
• Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM: Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. Pubmed
• http://en.wikipedia.org/wiki/Exemestane
• Giudici, D., et al.: J. Steroid Biochem., 30, 391 (1988)
• Evans, T.R.J., et al.: Cancer Res., 52, 5933 (1988)
• Zilembo, N., et al.: Brit. J. Cancer, 72, 1007 (1995)