ANASTROZOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H19N5
Molecular Weight	293.3669
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C#N)c1cc(cc(c1)C(C)(C)C#N)Cn2cncn2

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 35 Target ID: CHEMBL1978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19794821	Inhibitor 7728

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 411 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020541s029lbl.pdf	Palliative		Approved 8043	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 1601	inhibitor 1604 substrate 936	inhibitor 1702 substrate 1118

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 627 CYP1A2 1383 CYP3A 191	CYP1A2 972 CYP2A6 485 CYP2B6 616 CYP2C8 634 CYP2C19 910 CYP2E1 606 CYP3A5 367 UGT1A1 393 UGT1A3 397 UGT1A4 330 UGT1A6 289 UGT1A7 221 UGT1A8 266 UGT1A9 357 UGT1A10 273 UGT2B4 233 UGT2B7 362 UGT2B15 191 UGT2B17 203 P-gp 1400 BCRP 515

Drug as perpetrator

Target	Modality	Activity
CYP2A6 659	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	no
CYP2D6 1738	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	no
CYP2C9 1648	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	yes [Ki 10 uM]
CYP3A 271	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/25/5/598?ijkey=f5f4a077bb1bf0fceb9b8a924da966fe45108323&keytype2=tf_ipsecsha	yes [Ki 10 uM]
CYP1A2 1532	inhibitor 3045 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 616	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	low
CYP2C8 634	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	low
CYP2D6 1118	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	low
CYP3A4 1601	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	major
UGT1A4 330	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	major
CYP3A5 367	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	minor
UGT1A3 397	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	minor
UGT2B7 362	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	minor
BCRP 515	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/23712697/	no
CYP1A2 972	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
CYP2A6 485	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
CYP2C19 910	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
CYP2C9 936	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
CYP2E1 606	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A1 393	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A10 273	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A6 289	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A7 221	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A8 266	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT1A9 357	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT2B15 191	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT2B17 203	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
UGT2B4 233	substrate 3113 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014069/	no
P-gp 1400	substrate 3113 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
Aromatase and aromatase inhibitors.	2001	11791126
Third-generation aromatase inhibitors in the treatment of advanced breast cancer.	2001	11791122
New combinations with Herceptin in metastatic breast cancer.	2001	11694788
[Modern approaches to hormone therapy of breast cancer as a reflection of pathogenesis of the disease].	2001	11383456
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	11305952
[Development of a novel aromatase inhibitor, anastrozole (Arimidex)--its basic and clinical studies].	2001 Apr	11329794
Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer.	2001 Aug	12113022
Exemestane: new preparation. No tangible advance in metastatic breast cancer after tamoxifen failure.	2001 Aug	11718178
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
Where do selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) now fit into breast cancer treatment algorithms?	2001 Dec	11850229
Faslodex (ICI 182, 780), a novel estrogen receptor downregulator--future possibilities in breast cancer.	2001 Dec	11850227
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
Intracellular aromatase and its relevance to the pharmacological efficacy of aromatase inhibitors.	2001 Jan-Mar	11384878
Anastrozole: licence extension. No advantage over tamoxifen in advanced-stage breast cancer.	2001 Jun	11718168
Endocrine therapy in the treatment of metastatic breast cancer.	2001 Jun	11402439
The effect of aromatase inhibition on sex steroids, gonadotropins, and markers of bone turnover in older men.	2001 Jun	11397902
Aromatization mediates testosterone's short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men.	2001 Jun	11397860
[Aromatase inhibitors: anastrozole versus tamoxifen as first-ine therapy for advanced postmenopausal breast cancer].	2001 May	11398617
Aromatase inhibition and antiestrogen therapy in early breast cancer treatment and chemoprevention.	2001 May	11396362
[Evolvement of hormone therapy for breast cancer. Florence, March 14, 2001].	2001 May-Jun	11505951
Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma.	2001 Nov 1	11745278
Role of anti-aromatase agents in postmenopausal advanced breast cancer.	2001 Oct	11710624
Use of the aromatase inhibitor anastrozole in the treatment of patients with advanced prostate carcinoma.	2001 Oct 15	11596025
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
Estrogen as therapy for breast cancer.	2002	12100736
Estrogen receptor downregulators: new antihormonal therapy for advanced breast cancer.	2002	11911506
Gateways to Clinical Trials.	2002 Apr	12087878
Existing and emerging endocrine therapies for breast cancer.	2002 Apr	12080538
The oncology nurse's role in educating patients on endocrine therapy for metastatic breast cancer--focus on fulvestrant.	2002 Apr	12080536
Antiaromatase agents: evolving role in adjuvant therapy.	2002 Apr	12020394
Effects of aromatase inhibition on in vitro follicle and oocyte development analyzed by early preantral mouse follicle culture.	2002 Apr	11891927
Aromatase inhibitors for male infertility.	2002 Feb	11792932
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
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
Endocrine and clinical endpoints of exemestane as neoadjuvant therapy.	2002 Mar-Apr	11965226
Anti-aromatase agents in the treatment and prevention of breast cancer.	2002 Mar-Apr	11965225

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

ZD1033

Code

English

ANASTROZOLE [USP]

Common Name

English

ANASTROZOLE [USP-RS]

Common Name

English

ZD-1033

Code

English

ICI-D1033

Code

English

ANASTROZOLE [WHO-DD]

Common Name

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