U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H24O2
Molecular Weight 296.4034
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EXEMESTANE

SMILES

[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CC(=C)C4=CC(=O)C=C[C@]34C

InChI

InChIKey=BFYIZQONLCFLEV-DAELLWKTSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020753s009s011s012lbl.pdf

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. Breast cancer cell growth may be estrogen-dependent. Aromatase (exemestane) is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. 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, an effect also known as "suicide inhibition". Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on the adrenal biosynthesis of corticosteroids or aldosterone. This reduction in serum and tumor concentrations of estrogen delays tumor growth and disease progression. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme. Exemestane is marketed under the trade name Aromasin.

Originator

Curator's Comment: # Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
50.1 nM [IC50]
28.02 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Aromasin

Approved Use

AROMASIN is an aromatase inhibitor indicated for: adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to AROMASIN for completion of a total of five consecutive years of adjuvant hormonal therapy. the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy

Launch Date

1999
Primary
Aromasin

Approved Use

AROMASIN is an aromatase inhibitor indicated for: adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to AROMASIN for completion of a total of five consecutive years of adjuvant hormonal therapy. the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy

Launch Date

1999
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
16.1 ng/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EXEMESTANE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
36.4 ng × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EXEMESTANE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.9 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EXEMESTANE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
600 mg 1 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources: Page: p.678
unhealthy, 37-77
n = 4
Health Status: unhealthy
Condition: Breast cancer
Age Group: 37-77
Sex: F
Population Size: 4
Sources: Page: p.678
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources: Page: p.5935
healthy, 48 - 75
n = 3
Health Status: healthy
Age Group: 48 - 75
Sex: F
Population Size: 3
Sources: Page: p.5935
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 2252
Health Status: unhealthy
Condition: Breast cancer
Sex: F
Population Size: 2252
Sources: Page: p.4
Disc. AE: Myocardial infarction, Angina...
AEs leading to
discontinuation/dose reduction:
Myocardial infarction
Angina
Myocardial ischemia
Cardiac failure (0.4%)
Sources: Page: p.4
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Breast cancer
Sex: F
Sources: Page: p.1
Disc. AE: Bone density increased, Fetal damage...
AEs leading to
discontinuation/dose reduction:
Bone density increased
Fetal damage
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Cardiac failure 0.4%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 2252
Health Status: unhealthy
Condition: Breast cancer
Sex: F
Population Size: 2252
Sources: Page: p.4
Angina Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 2252
Health Status: unhealthy
Condition: Breast cancer
Sex: F
Population Size: 2252
Sources: Page: p.4
Myocardial infarction Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 2252
Health Status: unhealthy
Condition: Breast cancer
Sex: F
Population Size: 2252
Sources: Page: p.4
Myocardial ischemia Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.4
unhealthy
n = 2252
Health Status: unhealthy
Condition: Breast cancer
Sex: F
Population Size: 2252
Sources: Page: p.4
Bone density increased Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Breast cancer
Sex: F
Sources: Page: p.1
Fetal damage Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Breast cancer
Sex: F
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
Aromatase inhibitors.
2001
Future use of selective estrogen receptor modulators and aromatase inhibitors.
2001 Dec
Preliminary data from ongoing adjuvant aromatase inhibitor trials.
2001 Dec
Are differences in the available aromatase inhibitors and inactivators significant?
2001 Dec
The role of tamoxifen and aromatase inhibitors/inactivators in postmenopausal patients.
2001 Dec
Where do selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) now fit into breast cancer treatment algorithms?
2001 Dec
Adjuvant trials of aromatase inhibitors: determining the future landscape of adjuvant endocrine therapy.
2001 Dec
A summary of second-line randomized studies of aromatase inhibitors.
2001 Dec
Local endocrine effects of aromatase inhibitors within the breast.
2001 Dec
The impact of hormonal treatments on quality of life of patients with metastatic breast cancer.
2002
Tamoxifen resistant and refractory breast cancer: the value of aromatase inhibitors.
2002
Cost-effectiveness analysis of exemestane compared with megestrol in advanced breast cancer: a model for Europe and Australia.
2002
Aromatase inhibitors in breast cancer therapy.
2002 Apr
[The role of aromatase inhibitors in the treatment of breast neoplasms. An evaluation of clinical efficacy and the tolerability profile].
2002 Apr
Antiaromatase agents: evolving role in adjuvant therapy.
2002 Apr
New breast cancer drugs expand treatment options.
2002 Apr
Plasma fibrin D-dimer levels correlate with tumour volume, progression rate and survival in patients with metastatic breast cancer.
2002 Feb 1
[Aromatase inhibitors of the 3rd generation. What can the "pill against breast cancer" really do?].
2002 Jan 31
[Late phase II study of exemestane in postmenopausal patients with breast cancer resistant to anti-estrogenic agents].
2002 Jul
[Phase I multiple-dose administration study of exemestane in postmenopausal women].
2002 Jul
Letrozole for the management of breast cancer.
2002 Jun
Current status and future potential role of exemestane in the treatment of early and advanced breast cancer (Review).
2002 Jun
Aromatase inhibitors in breast cancer.
2002 Mar
Endocrine and clinical endpoints of exemestane as neoadjuvant therapy.
2002 Mar-Apr
Anti-aromatase agents in the treatment and prevention of breast cancer.
2002 Mar-Apr
An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane.
2002 Nov 1
The evolving role of aromatase inhibitors in breast cancer.
2002 Oct
Sequencing of endocrine therapies in breast cancer--integration of recent data.
2002 Oct
New generation aromatase inhibitors--from the advanced to the adjuvant setting.
2002 Oct
[Perspectives for the hormonal therapy of breast cancer].
2003
Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer.
2003
8th international conference: primary therapy of early breast cancer, St Gallen, Switzerland, March 12-15 2003.
2003
Update on the current use of hormonals as therapy in advanced breast cancer.
2003 Apr
The role of aromatase inhibitors in early breast cancer.
2003 Apr
Aromatase inhibitors in early breast cancer treatment.
2003 Aug
The role of aromatase inhibitors in the treatment of metastatic breast cancer.
2003 Aug
Pharmacokinetics of third-generation aromatase inhibitors.
2003 Aug
Aromatase inhibitors: mechanism of action and role in the treatment of breast cancer.
2003 Aug
Should aromatase inhibitors replace tamoxifen?
2003 Aug
A comparison of the efficacy of aromatase inhibitors in second-line treatment of metastatic breast cancer.
2003 Aug
The current status of aromatase inhibitors in the management of breast cancer.
2003 Aug
Clinical differences among the aromatase inhibitors.
2003 Jan
Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors.
2003 Jan
[Pharmacological and clinical profile of exemestane (Aromasin), a novel irreversible aromatase inhibitor].
2003 Oct
Celecoxib anti-aromatase neoadjuvant (CAAN) trial for locally advanced breast cancer: preliminary report.
2003 Sep
Aromatase inhibitors as adjuvant therapies in patients with breast cancer.
2003 Sep
The intratumoral aromatase model: studies with aromatase inhibitors and antiestrogens.
2003 Sep
[Clinical trial on exemestane in the treatment of postmenopausal women with advanced breast cancer].
2003 Sep
Exemestane seems to stimulate tumour growth in men with prostate carcinoma.
2003 Sep
Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer.
2003 Sep
Patents

Sample Use Guides

One 25 mg tablet once daily after a meal
Route of Administration: Oral
Exemestane (28 uM) inhibits the growth of MCF‑7 cells.
Name Type Language
EXEMESTANE
HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
EXEMESTANE [ORANGE BOOK]
Common Name English
FCE-24304
Code English
EXEMESTANE [USP-RS]
Common Name English
Exemestane [WHO-DD]
Common Name English
exemestane [INN]
Common Name English
EXEMESTANE [VANDF]
Common Name English
EXEMESTANE [JAN]
Common Name English
EXEMESTANE [USP MONOGRAPH]
Common Name English
EXEMESTANE [USAN]
Common Name English
EXEMESTANE [MI]
Common Name English
ANDROSTA-1,4-DIENE-3,17-DIONE, 6-METHYLENE-
Systematic Name English
NSC-758907
Code English
EXEMESTANE [MART.]
Common Name English
EXEMESTANE [HSDB]
Common Name English
EXEMESTANE [EP MONOGRAPH]
Common Name English
6-Methyleneandrosta-1,4-diene-3,17-dione
Systematic Name English
AROMASIN
Brand Name English
FCE24304
Code English
PNU-155971
Code English
Classification Tree Code System Code
LIVERTOX NBK548926
Created by admin on Sat Dec 16 17:25:05 GMT 2023 , Edited by admin on Sat Dec 16 17:25:05 GMT 2023
NDF-RT N0000175080
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WHO-VATC QL02BG06
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FDA ORPHAN DRUG 60191
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WHO-ATC L02BG06
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NDF-RT N0000175563
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NCI_THESAURUS C2017
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Code System Code Type Description
EPA CompTox
DTXSID5023037
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PRIMARY
PUBCHEM
60198
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PRIMARY
ChEMBL
CHEMBL1200374
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PRIMARY
INN
6770
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PRIMARY
WIKIPEDIA
EXEMESTANE
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PRIMARY
HSDB
7463
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PRIMARY
IUPHAR
7073
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PRIMARY
DRUG BANK
DB00990
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PRIMARY
MERCK INDEX
m5224
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PRIMARY Merck Index
DAILYMED
NY22HMQ4BX
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PRIMARY
CHEBI
4953
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PRIMARY
RXCUI
258494
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PRIMARY RxNorm
USAN
LL-46
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PRIMARY
NCI_THESAURUS
C1097
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PRIMARY
CAS
107868-30-4
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PRIMARY
EVMPD
SUB07492MIG
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PRIMARY
LACTMED
Exemestane
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PRIMARY
SMS_ID
100000092298
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PRIMARY
FDA UNII
NY22HMQ4BX
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PRIMARY
RS_ITEM_NUM
1269050
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PRIMARY
NSC
758907
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PRIMARY
MESH
C056516
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PRIMARY
DRUG CENTRAL
1122
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PRIMARY