EXEMESTANE

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 Search

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
Sources: http://www.drugbank.ca/drugs/DB00990
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 19A1 39 Target ID: CHEMBL1978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22951074	Inhibitor 8297		50.1 nM [IC50]
MCF7 21 Target ID: CHEMBL387 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25738757	Inhibitor 8297		28.02 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Estrogen-receptor positive early breast cancer 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020753s009s011s012lbl.pdf	Primary		Approved 8429	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
Advanced breast cancer in postmenopausal women 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020753s009s011s012lbl.pdf	Primary		Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
16.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/14671195	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

Value	Dose	Co-administered	Analyte	Population
36.4 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/14671195	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/14671195	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/9823425/ Page: p.678	unhealthy, 37-77 n = 4 Health Status: unhealthy Condition: Breast cancer Age Group: 37-77 Sex: F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/9823425/ Page: p.678	Sources: https://pubmed.ncbi.nlm.nih.gov/9823425/ Page: p.678
800 mg single, oral Highest studied dose Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1394219 Page: p.5935	healthy, 48 - 75 n = 3 Health Status: healthy Age Group: 48 - 75 Sex: F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/1394219 Page: p.5935	Sources: https://pubmed.ncbi.nlm.nih.gov/1394219 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.4	unhealthy n = 2252 Health Status: unhealthy Condition: Breast cancer Sex: F Population Size: 2252 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.4	Disc. AE: Myocardial infarction, Angina... AEs leading to discontinuation/dose reduction: Myocardial infarction Angina Myocardial ischemia Cardiac failure (0.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Breast cancer Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.1	Disc. AE: Bone density increased, Fetal damage... AEs leading to discontinuation/dose reduction: Bone density increased Fetal damage Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.4	unhealthy n = 2252 Health Status: unhealthy Condition: Breast cancer Sex: F Population Size: 2252 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.4	unhealthy n = 2252 Health Status: unhealthy Condition: Breast cancer Sex: F Population Size: 2252 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.4	unhealthy n = 2252 Health Status: unhealthy Condition: Breast cancer Sex: F Population Size: 2252 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.4	unhealthy n = 2252 Health Status: unhealthy Condition: Breast cancer Sex: F Population Size: 2252 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Breast cancer Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Breast cancer Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020753s020lbl.pdf Page: p.1

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4953	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4953
ChemicalBook	CB5760314	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5760314
Selleck Chemicals	Exemestane	http://www.selleckchem.com/products/Exemestane.html
ZINC	ZINC000003973334	http://zinc15.docking.org/substances/ZINC000003973334
eMolecules	2726151	https://www.emolecules.com/cgi-bin/more?vid=2726151

PubMed

Title	Date	PubMed
Current role of endocrine therapy in the management of breast cancer.	2002	12459706
Evolving uses of hormonal agents for breast cancer therapy.	2002	12117074
The impact of hormonal treatments on quality of life of patients with metastatic breast cancer.	2002	12117073
Aromatase inhibitors in breast cancer therapy.	2002 Apr	12113240
The role of aromatase inactivators in the treatment of breast cancer.	2002 Aug	12202980
[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer].	2002 Jul	12146001
[Phase I multiple-dose administration study of exemestane in postmenopausal women].	2002 Jul	12146000
[Phase I single-dose administration study of exemestane in postmenopausal women].	2002 Jul	12145999
Exemestane: a potent irreversible aromatase inactivator and a promising advance in breast cancer treatment.	2002 Jun	12113050
Neoadjuvant endocrine therapy of breast cancer: a surgical perspective.	2002 Nov	12441257
An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane.	2002 Nov 1	12404296
Exemestane: treatment of breast cancer with selective inactivation of aromatase.	2002 Nov 15	12455303
The evolving role of aromatase inhibitors in breast cancer.	2002 Oct	12402060
Sequencing of endocrine therapies in breast cancer--integration of recent data.	2002 Oct	12353821
New generation aromatase inhibitors--from the advanced to the adjuvant setting.	2002 Oct	12353818
Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.	2003	14535531
[Perspectives for the hormonal therapy of breast cancer].	2003	12975659
Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer.	2003	12897330
8th international conference: primary therapy of early breast cancer, St Gallen, Switzerland, March 12-15 2003.	2003	12817991
Aromatase inhibitors for treatment of postmenopausal patients with breast cancer.	2003 Apr	12722879
Update on the current use of hormonals as therapy in advanced breast cancer.	2003 Apr	12679730
The role of aromatase inhibitors in early breast cancer.	2003 Apr	12594939
Aromatase inhibitors in early breast cancer treatment.	2003 Aug	14513436
The role of aromatase inhibitors in the treatment of metastatic breast cancer.	2003 Aug	14513435
Pharmacokinetics of third-generation aromatase inhibitors.	2003 Aug	14513434
Aromatase inhibitors: mechanism of action and role in the treatment of breast cancer.	2003 Aug	14513432
Should aromatase inhibitors replace tamoxifen?	2003 Aug	12966738
Emerging role of aromatase inhibitors in the adjuvant setting.	2003 Aug	12902874
Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy.	2003 Aug	12902873
A comparison of the efficacy of aromatase inhibitors in second-line treatment of metastatic breast cancer.	2003 Aug	12902872
The current status of aromatase inhibitors in the management of breast cancer.	2003 Aug	12875605
[Treatment of advanced metastatic breast cancer with exemestane, a multicenter randomized controlled study of 195 cases].	2003 Feb 10	12812657
Clinical differences among the aromatase inhibitors.	2003 Jan	12538503
Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors.	2003 Jan	12538502
Is there a benefit by the sequence anastrozole-formestane for postmenopausal metastatic breast cancer women?	2003 Jul	12943750
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	12926095
Long-term toxicities of selective estrogen-receptor modulators and antiaromatase agents.	2003 May	12800793
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	12684675
A roundtable discussion of aromatase inhibitors as therapy for breast cancer.	2003 May-Jun	12752630
Economic evaluation of antiaromatase agents in the second-line treatment of metastatic breast cancer.	2003 Nov	12883965
[Pharmacological and clinical profile of exemestane (Aromasin), a novel irreversible aromatase inhibitor].	2003 Oct	14501171
Celecoxib anti-aromatase neoadjuvant (CAAN) trial for locally advanced breast cancer: preliminary report.	2003 Sep	14623542
An integrated view of aromatase and its inhibition.	2003 Sep	14623539
Aromatase inhibitors versus tamoxifen for management of postmenopausal breast cancer in the advanced disease and neoadjuvant settings.	2003 Sep	14623527
Aromatase inhibitors as adjuvant therapies in patients with breast cancer.	2003 Sep	14623526
Neoadjuvant comparisons of aromatase inhibitors and tamoxifen: pretreatment determinants of response and on-treatment effect.	2003 Sep	14623525
The intratumoral aromatase model: studies with aromatase inhibitors and antiestrogens.	2003 Sep	14623522
[Clinical trial on exemestane in the treatment of postmenopausal women with advanced breast cancer].	2003 Sep	14575582
Exemestane seems to stimulate tumour growth in men with prostate carcinoma.	2003 Sep	12957469
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	12954578

Patents

Sample Use Guides

In Vivo Use Guide

One 25 mg tablet once daily after a meal

Route of Administration: Oral

In Vitro Use Guide

Exemestane (28 uM) inhibits the growth of MCF‑7 cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:25:02 GMT 2023` Edited by `admin` on `Sat Dec 16 17:25:02 GMT 2023`
Record UNII	NY22HMQ4BX
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

EXEMESTANE

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