ANASTROZOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H19N5
Molecular Weight	293.3663
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C#N)C1=CC(=CC(CN2C=NC=N2)=C1)C(C)(C)C#N

InChI

InChIKey=YBBLVLTVTVSKRW-UHFFFAOYSA-N

InChI=1S/C17H19N5/c1-16(2,9-18)14-5-13(8-22-12-20-11-21-22)6-15(7-14)17(3,4)10-19/h5-7,11-12H,8H2,1-4H3

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020541s029lbl.pdf

Anastrozole (marketed under the trade name Arimidex by AstraZeneca) is a drug indicated in the treatment of breast cancer in post-menopausal women. It is used both in adjuvant therapy (i.e. following surgery) and in metastatic breast cancer. It decreases the amount of estrogens that the body makes. Anastrozole belongs in the class of drugs known as aromatase inhibitors. It inhibits the enzyme aromatase, which is responsible for converting androgens (produced by women in the adrenal glands) to estrogens. The growth of many cancers of the breast is stimulated or maintained by estrogens. In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme. Anastrozole is a selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 19A1 38 Target ID: CHEMBL1978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19794821	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 431 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020541s029lbl.pdf	Palliative		Approved 8360	ARIMIDEX Approved Use Anastrozole is an aromatase inhibitor indicated for: Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer ( 1.1) First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer ( 1.2) Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole ( 1.3) 1.1 Adjuvant Treatment Anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. 1.2 First-Line Treatment Anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. 1.3 Second-Line Treatment Anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets. Launch Date 8.2002241E11

C_max

Value	Dose	Co-administered	Analyte	Population
39.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19470631	1 mg 1 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ANASTROZOLE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
648 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19470631	1 mg 1 times / day steady-state, oral dose: 1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ANASTROZOLE plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	inhibitor 1752 substrate 1010	inhibitor 1837 substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 704 CYP1A2 1509 CYP3A 211	CYP1A2 1032 CYP2A6 523 CYP2B6 660 CYP2C8 688 CYP2C19 985 CYP2E1 648 CYP3A5 391 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 290 UGT2B4 249 UGT2B7 389 UGT2B15 203 UGT2B17 213 P-gp 1527 BCRP 555

Drug as perpetrator

Target	Modality	Activity
CYP2A6 736	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	no
CYP2D6 1875	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	no
CYP2C9 1803	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	yes [Ki 10 uM]
CYP3A 295	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	yes [Ki 10 uM]
CYP1A2 1673	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	yes [Ki 8 uM]

Drug as victim

Target	Modality	Activity
CYP2B6 660	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	low
CYP2C8 688	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	low
CYP2D6 1193	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	low
CYP3A4 1709	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	major
UGT1A4 347	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	major
CYP3A5 391	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	minor
UGT1A3 422	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	minor
UGT2B7 389	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	minor
BCRP 555	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/23712697/	no
CYP1A2 1032	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
CYP2A6 523	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
CYP2C19 985	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
CYP2C9 1010	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
CYP2E1 648	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A1 418	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A10 290	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A6 307	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A7 236	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A8 283	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A9 380	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT2B15 203	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT2B17 213	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT2B4 249	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/23712697/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306492/#bcp13130-bib-0009	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2704	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2704
ChemicalBook	CB3121715	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3121715
Selleck Chemicals	Anastrozole	http://www.selleckchem.com/products/Anastrozole.html
ZINC	ZINC000000000941	http://zinc15.docking.org/substances/ZINC000000000941
eMolecules	27516220	https://www.emolecules.com/cgi-bin/more?vid=27516220
eMolecules	901391	https://www.emolecules.com/cgi-bin/more?vid=901391

PubMed

Title	Date	PubMed
Pure antiestrogens and breast cancer.	2001	11922402
Aromatase inhibitors.	2001	11900315
Breast cancer chemoprevention: beyond tamoxifen.	2001	11250754
Estrogenic upregulation of DNA polymerase beta in oocytes of preovulatory ovine follicles.	2001 Apr	11241778
Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer.	2001 Aug	12113022
Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the 'Arimidex and tamoxifen alone or in combination' (ATAC) trial.	2001 Aug 3	11487258
Promising results for Arimidex and Femara.	2001 Dec	12113080
Future use of selective estrogen receptor modulators and aromatase inhibitors.	2001 Dec	11916232
The role of tamoxifen and aromatase inhibitors/inactivators in postmenopausal patients.	2001 Dec	11916225
A summary of second-line randomized studies of aromatase inhibitors.	2001 Dec	11850214
Biological and clinical effects of aromatase inhibitors in neoadjuvant therapy.	2001 Dec	11850213
HER-2 amplification impedes the antiproliferative effects of hormone therapy in estrogen receptor-positive primary breast cancer.	2001 Dec 1	11731427
[Endometriosis and aromatase inhibitor].	2001 Jan	11235156
Differential regulation of gonadotropin secretion by testosterone in the human male: absence of a negative feedback effect of testosterone on follicle-stimulating hormone secretion.	2001 Jan	11231978
Intracellular aromatase and its relevance to the pharmacological efficacy of aromatase inhibitors.	2001 Jan-Mar	11384878
Endocrine therapy in the treatment of metastatic breast cancer.	2001 Jun	11402439
The effect of anastrozole on the single-dose pharmacokinetics and anticoagulant activity of warfarin in healthy volunteers.	2001 May	11422000
Aromatase inhibition and antiestrogen therapy in early breast cancer treatment and chemoprevention.	2001 May	11396362
Is anastrozole superior to tamoxifen as first-line therapy for advanced breast cancer?	2001 May 1	11331346
Is anastrozole superior to tamoxifen as first-line therapy for advanced breast cancer?	2001 May 1	11331344
Is anastrozole superior to tamoxifen as first-line therapy for advanced breast cancer?	2001 May 1	11331342
Is anastrozole superior to tamoxifen as first-line therapy for advanced breast cancer?	2001 May 1	11331341
Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still achievable?	2001 Nov	11822752
Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma.	2001 Nov 1	11745278
Tamoxifen vs the aromatase inhibitors: news from San Antonio, 2001.	2001 Nov-Dec	11807416
Aromatase inhibitors and inactivators in breast cancer.	2001 Oct 20	11668120
Advances in aromatase inhibition: clinical efficacy and tolerability in the treatment of breast cancer.	2001 Sep	11555572
Aromatase, aromatase inhibitors, and breast cancer.	2001 Sep-Oct	11550075
Finding the needle in the haystack: why high-throughput screening is good for your health.	2002	12100740
Estrogen as therapy for breast cancer.	2002	12100736
Recent advances in breast cancer (the Twenty-fourth San Antonio Breast Cancer Symposium, December, 2001).	2002	11999142
Tamoxifen resistant and refractory breast cancer: the value of aromatase inhibitors.	2002	11929341
Aromatase inhibitors continue their ATAC on tamoxifen.	2002	11927281
Gateways to Clinical Trials.	2002 Apr	12087878
The oncology nurse's role in educating patients on endocrine therapy for metastatic breast cancer--focus on fulvestrant.	2002 Apr	12080536
Short-term effects of anastrozole treatment on insulin-like growth factor system in postmenopausal advanced breast cancer patients.	2002 Apr	11983488
Effects of aromatase inhibition on in vitro follicle and oocyte development analyzed by early preantral mouse follicle culture.	2002 Apr	11891927
Fulvestrant.	2002 Feb	11829719
Hormones 'R' us.	2002 Jan	11899355
Endocrine effects of nonsteroidal aromatase inhibitors and their clinical impact.	2002 Jul 1	12089238
Letrozole for the management of breast cancer.	2002 Jun	12113048
[Antiestrogen therapy in the treatment of breast neoplasms].	2002 Jun	12063440
Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial.	2002 Jun 22	12090977
Aromatase inhibitors for the endocrine adjuvant treatment of breast cancer.	2002 Jun 22	12090973
Experience of hormonal therapy with anastrozole for previously treated metastatic breast cancer.	2002 Mar	11908256
Aromatase inhibitors in breast cancer.	2002 Mar	11854020
Detection of aromatase inhibitors in vitro using rat ovary microsomes.	2002 Mar 24	11879982
Endocrine and clinical endpoints of exemestane as neoadjuvant therapy.	2002 Mar-Apr	11965226
Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy.	2002 May	12058236

Patents

Sample Use Guides

In Vivo Use Guide

One 1 mg tablet taken once daily

Route of Administration: Oral

In Vitro Use Guide

Anastrozole, aromatase inhibitor was added at a concentration of 200 and 300 μg/mL to the endometrioma cells. The use of anastrozole significantly inhibited the growth of endometrioma cells, and estradiol secretion.

Name

Type

Language

ANASTROZOLE

Official Name

English

ANASTROZOLE [HSDB]

Common Name

English

ANASTROZOLE [ORANGE BOOK]

Common Name

English

ANASTROZOLE [MART.]

Common Name

English

Anastrozole [WHO-DD]

Common Name

English

ZD1033

Code

English

ANASTROZOLE [USP IMPURITY]

Common Name

English

ANASTROZOLE [USP-RS]

Common Name

English

ZD-1033

Code

English

ICI-D1033

Code

English

ANASTROZOLE [JAN]

Common Name

English

NSC-759855

Code

English

ANASTROZOLE [EP MONOGRAPH]

Common Name

English

ANASTROZOLE [MI]

Common Name

English

NSC-719344

Code

English

anastrozole [INN]

Common Name

English

1,3-BENZENEDIACETONITRILE,.ALPHA.,.ALPHA.,.ALPHA.',.ALPHA.'-TETRAMETHYL-5-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-

Common Name

English

ICI D1033

Code

English

ARIMIDEX

Brand Name

English

ANASTROZOLE [USP MONOGRAPH]

Common Name

English

RVG-106400

Common Name

English

ANASTROZOLE [USAN]

Common Name

English

.ALPHA.,.ALPHA.,.ALPHA.',.ALPHA.'-TETRAMETHYL-5-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-M-BENZENEDIACETONITRILE

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000175563