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

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H24O2
Molecular Weight 296.4041
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EXEMESTANE

SMILES

C=C1C[C@@]2([H])[C@]3([H])CCC(=O)[C@@]3(C)CC[C@]2([H])[C@@]4(C)C=CC(=O)C=C14

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

9.4037757E11
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

9.4037757E11
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
Current role of endocrine therapy in the management of breast cancer.
2002
McCune-Albright syndrome--the German experience.
2002
The role of aromasin in the hormonal therapy of breast cancer.
2002
Sequencing of hormonal therapy in postmenopausal women with metastatic breast cancer.
2002
Evolving uses of hormonal agents for breast cancer therapy.
2002
The role of aromatase inactivators in the treatment of breast cancer.
2002 Aug
Overview of the pharmacology of the aromatase inactivator exemestane.
2002 Jul
[Late phase II study of exemestane in postmenopausal patients with breast cancer resistant to anti-estrogenic agents].
2002 Jul
Recent advances in aromatase inhibitor therapy for breast cancer.
2002 Jun
Neoadjuvant endocrine therapy of breast cancer: a surgical perspective.
2002 Nov
An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane.
2002 Nov 1
Exemestane: treatment of breast cancer with selective inactivation of aromatase.
2002 Nov 15
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
Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.
2003
[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
Aromatase inhibitors for treatment of postmenopausal patients with breast cancer.
2003 Apr
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
Emerging role of aromatase inhibitors in the adjuvant setting.
2003 Aug
Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy.
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
[Treatment of advanced metastatic breast cancer with exemestane, a multicenter randomized controlled study of 195 cases].
2003 Feb 10
Clinical differences among the aromatase inhibitors.
2003 Jan
Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors.
2003 Jan
Is there a benefit by the sequence anastrozole-formestane for postmenopausal metastatic breast cancer women?
2003 Jul
Bone turnover markers and insulin-like growth factor components in metastatic breast cancer: results from a randomised trial of exemestane vs megestrol acetate.
2003 Jul-Aug
Long-term toxicities of selective estrogen-receptor modulators and antiaromatase agents.
2003 May
Could exemestane affect insulin-like growth factors, interleukin 6 and bone metabolism in postmenopausal advanced breast cancer patients after failure on aminoglutethimide, anastrozole or letrozole?
2003 May
A roundtable discussion of aromatase inhibitors as therapy for breast cancer.
2003 May-Jun
Economic evaluation of antiaromatase agents in the second-line treatment of metastatic breast cancer.
2003 Nov
[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
An integrated view of aromatase and its inhibition.
2003 Sep
Aromatase inhibitors versus tamoxifen for management of postmenopausal breast cancer in the advanced disease and neoadjuvant settings.
2003 Sep
Aromatase inhibitors as adjuvant therapies in patients with breast cancer.
2003 Sep
Neoadjuvant comparisons of aromatase inhibitors and tamoxifen: pretreatment determinants of response and on-treatment effect.
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 [INN]
Common Name English
EXEMESTANE [WHO-DD]
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 394
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
NDF-RT N0000175080
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
WHO-VATC QL02BG06
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
FDA ORPHAN DRUG 60191
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
WHO-ATC L02BG06
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
NDF-RT N0000175563
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
NCI_THESAURUS C2017
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
Code System Code Type Description
EPA CompTox
107868-30-4
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
PUBCHEM
60198
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
ChEMBL
CHEMBL1200374
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
INN
6770
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
USP_CATALOG
1269050
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY USP-RS
WIKIPEDIA
EXEMESTANE
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
HSDB
7463
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
IUPHAR
7073
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
DRUG BANK
DB00990
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
MERCK INDEX
M5224
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY Merck Index
RXCUI
258494
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C1097
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
CAS
107868-30-4
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
EVMPD
SUB07492MIG
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
LACTMED
Exemestane
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
FDA UNII
NY22HMQ4BX
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
MESH
C056516
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY
DRUG CENTRAL
1122
Created by admin on Fri Jun 25 21:06:19 UTC 2021 , Edited by admin on Fri Jun 25 21:06:19 UTC 2021
PRIMARY