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

Molecular Formula C20H24O2
Molecular Weight 296.4041
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: 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

TargetsConditions

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

940377600000
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

940377600000
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:
unhealthy, 37-77
Health Status: unhealthy
Age Group: 37-77
Sex: F
Sources:
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
healthy, 48 - 75
Health Status: healthy
Age Group: 48 - 75
Sex: F
Sources:
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:
unhealthy
Disc. AE: Bone density increased, Fetal damage...
AEs leading to
discontinuation/dose reduction:
Bone density increased
Fetal damage
Sources:
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:
unhealthy
Disc. AE: Myocardial infarction, Angina...
AEs leading to
discontinuation/dose reduction:
Myocardial infarction
Angina
Myocardial ischemia
Cardiac failure (0.4%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
PubMed

PubMed

TitleDatePubMed
Third-generation aromatase inhibitors in the treatment of advanced breast cancer.
2001
[Modern approaches to hormone therapy of breast cancer as a reflection of pathogenesis of the disease].
2001
Update on endocrine aspects of breast cancer: report from the 23rd San Antonio Breast Cancer Symposium, San Antonio, Texas, USA, 6-9 December 2000.
2001
Breast cancer chemoprevention: beyond tamoxifen.
2001
Metastatic breast cancer: understanding current management options.
2001 Apr
Steroidal side effects of exemestane.
2001 Apr 1
Nonsteroidal and steroidal aromatase inhibitors in breast cancer.
2001 Aug
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
A summary of second-line randomized studies of aromatase inhibitors.
2001 Dec
High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy.
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
Endocrine therapy in the treatment of metastatic breast cancer.
2001 Jun
Reproductive toxicity of exemestane, an antitumoral aromatase inactivator, in rats and rabbits.
2001 Mar-Apr
Aromatase, aromatase inhibitors, and breast cancer.
2001 Sep-Oct
Tamoxifen resistant and refractory breast cancer: the value of aromatase inhibitors.
2002
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
The evolving role of aromatase inhibitors in breast cancer.
2002 Oct
Sequencing of endocrine therapies in breast cancer--integration of recent data.
2002 Oct
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
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
[Pharmacological and clinical profile of exemestane (Aromasin), a novel irreversible aromatase inhibitor].
2003 Oct
Neoadjuvant comparisons of aromatase inhibitors and tamoxifen: pretreatment determinants of response and on-treatment effect.
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 Fri Jun 25 21:06:19 UTC 2021
Edited
by admin
on Fri Jun 25 21:06:19 UTC 2021
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 [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
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
DERIVATIVE -> PARENT
PLASMA; URINE
EXCRETED UNCHANGED
URINE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
BINDER->LIGAND
BINDING
DERIVATIVE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
MAJOR
PLASMA; URINE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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