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

Molecular Formula C20H24O2
Molecular Weight 296.4034
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

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
[Modern approaches to hormone therapy of breast cancer as a reflection of pathogenesis of the disease].
2001
Steroidal side effects of exemestane.
2001 Apr 1
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
Local endocrine effects of aromatase inhibitors within the breast.
2001 Dec
Cost-effectiveness analysis of exemestane compared with megestrol in patients with advanced breast carcinoma.
2001 Feb 1
Aromatase inhibitors in the treatment and prevention of breast cancer.
2001 Feb 1
Adjuvant exemestane therapy after 5 years of tamoxifen: rationale for the NSABP B-33 trial.
2001 May
Aromatase, aromatase inhibitors, and breast cancer.
2001 Sep-Oct
McCune-Albright syndrome--the German experience.
2002
The role of aromasin in the hormonal therapy of breast cancer.
2002
Estrogen as therapy for breast cancer.
2002
[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
Exemestane, a new steroidal aromatase inhibitor of clinical relevance.
2002 Jul 18
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
Endocrine and clinical endpoints of exemestane as neoadjuvant therapy.
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
New generation aromatase inhibitors--from the advanced to the adjuvant setting.
2002 Oct
The role of aromatase inhibitors in the treatment of metastatic breast cancer.
2003 Aug
Pharmacokinetics of third-generation aromatase inhibitors.
2003 Aug
[Pharmacological and clinical profile of exemestane (Aromasin), a novel irreversible aromatase inhibitor].
2003 Oct
Aromatase inhibitors versus tamoxifen for management of postmenopausal breast cancer in the advanced disease and neoadjuvant settings.
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:25:02 UTC 2023
Edited
by admin
on Sat Dec 16 17:25:02 UTC 2023
Record UNII
NY22HMQ4BX
Record Status Validated (UNII)
Record Version
  • Download
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 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
NDF-RT N0000175080
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
WHO-VATC QL02BG06
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
FDA ORPHAN DRUG 60191
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
WHO-ATC L02BG06
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
NDF-RT N0000175563
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
NCI_THESAURUS C2017
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID5023037
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
PUBCHEM
60198
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
ChEMBL
CHEMBL1200374
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
INN
6770
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
WIKIPEDIA
EXEMESTANE
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
HSDB
7463
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
IUPHAR
7073
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
DRUG BANK
DB00990
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
MERCK INDEX
m5224
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY Merck Index
DAILYMED
NY22HMQ4BX
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
CHEBI
4953
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
RXCUI
258494
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY RxNorm
USAN
LL-46
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
NCI_THESAURUS
C1097
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
CAS
107868-30-4
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
EVMPD
SUB07492MIG
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
LACTMED
Exemestane
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
SMS_ID
100000092298
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
FDA UNII
NY22HMQ4BX
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
RS_ITEM_NUM
1269050
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
NSC
758907
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
MESH
C056516
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
DRUG CENTRAL
1122
Created by admin on Sat Dec 16 17:25:05 UTC 2023 , Edited by admin on Sat Dec 16 17:25:05 UTC 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
DERIVATIVE -> PARENT
PLASMA; URINE
EXCRETED UNCHANGED
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METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
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BINDING
DERIVATIVE -> PARENT
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METABOLIC ENZYME -> SUBSTRATE
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

IN THE HEALTHY WOMEN

Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION

Tmax PHARMACOKINETIC ORAL ADMINISTRATION

IN THE WOMEN WITH BREAST CANCER