(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 ID: 864
• Molecular Formular: C20H24O2
• Molecular Mass: 296.40336
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: (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 Traditional name: exemestane
• Brand Name: Aromasin; Exemestance
• Synonyms: 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

Database IDs

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

CALCULATED PROPERTIES

JChem

• Acid pKa: 19.957294
• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 3.8661478
• LogD (pH = 7.4): 3.8661478
• Log P: 3.8661478
• Molar Refractivity: 89.0269 cm^3
• Polarizability: 34.07716 Å^3
• Polar Surface Area: 34.14 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.67
• LOG S: -4.64
• Solubility (Water): 6.83e-03 g/l

PROPERTIES

Physical Property

• Solubility: Acetonitrile; Chloroform; DMSO; DMSO: ≥20 mg/mL; Non-soluble
• Apperance: Off-White Solid; white to off-white powder
• Melting Point: 191-193°C
• Optical Rotation: [α]/D +250 to +300°, c = 1 in methanol
• Hydrophobicity(logP): 3.7

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• European Hazard Symbols: Nature polluting (N); Toxic (T)
• German water hazard class: 3
• Risk Statements: 60-61-51
• Safety Statements: 53-22-36/37-57
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H319-H360
• GHS Precautionary statements: P201-P305 + P351 + P338-P308 + P313
• Storage Temperature: room temp

Pharmacology Properties

• Target: aromatase enzyme

Product Information

• Purity: ≥98% (HPLC); 96%; 98%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C20H24O2

DETAILS

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).

REFERENCES

• 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)