CAS 107868-30-4|(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|exemestane|exemestane|Exemestano [INN-Spanish]|Exemestance|Exemestane...

General Information

Structure

Molecular Formula

C₂₀H₂₄O₂

Molecular Mass

296.40336

Exact Mass

296.17763001

Charge

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

Canonic 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

Isomeric 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

Calculated Properties

JChem

LogD (pH = 7.4)

3.87

LogD (pH = 5.5)

3.87

Log P

3.87

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

-5.04

Polar Surface Area

34.14

Polarizability

33.70

Molar Refractivity

89.03

LOG S

-5.18

Data Source

Names and Identifiers

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[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-diene-5,14-dione (3aS,3bR,9aR,9bS,11aS)-9a,11a-dimethyl-5-methylidene-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-dione

Synonyms

Exemestano [INN-Spanish]exemestaneExemestaneExemestanum [INN-Latin]Aromasin6-Methyleneandrosta-1,4-diene-3,17-dioneExemestaneFCE-243046-Methylene-androsta-1,4-diene-3,17-dioneexemestane6-methyleneandrosta-1,4-diene-3,17-dioneExemestane

IUPAC Traditional name

exemestane

Brand Name

AromasinExemestance

International Nonproprietary Name (INN)

exemestaneexemestanumexemestano

Names and Identifiers

Registration numbers

CAS Number

107868-30-4

MDL Number

MFCD00866994

PubChem SID

4650824316096432799437373

PubChem CID

60198

MassBank Database

EA066108EA066114EA066102EA066107EA066112EA066101EA066113EA066110EA066105EA066109EA066111EA066104EA066103EA066106

KEGG ID

C08162

Drug Central Database

1,122

CHEMBL

CHEMBL1200374

Reaxys Registry

6609645

MetaboLights Database

MTBLS1693MTBLS2145

CHEBI ID

CHEBI:4953

PubMed Citation Links

SureChEMBL Database

DrugBank ID

Wikipedia Title

ACToR Database

CompTox Database

Protein Data Bank

KEGG DRUG Database

BindingDB Database

Registration numbers

Properties

Pharmacology Properties

Target

aromatase enzyme

Properties

Related Proteins

PDB Bank

3S7S

Related Proteins

Molecular Spectra

No Data Available

Click here to submit data

Molecule 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.

TRC

E957000

An antineoplastic (hormonal).

ChEBI

CHEBI:4953

A 17-oxo steroid that is androsta-1,4-diene-3,17-dione in which the hydrogens at position 6 are replaced by a double bond to a methylene group. A selective inhibitor of the aromatase (oestrogen synthase) system, it is used in the treatment of advanced breast cancer.

Molecule Details

References

PubChem Literature

From Data Sources

• 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

• 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

• http://en.wikipedia.org/wiki/Exemestane

• Giudici, D., et al.: J. Steroid Biochem., 30, 391 (1988)

• Zilembo, N., et al.: Brit. J. Cancer, 72, 1007 (1995)

• Evans, T.R.J., et al.: Cancer Res., 52, 5933 (1988)

References