LETROZOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H11N5
Molecular Weight	285.3027
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N#CC1=CC=C(C=C1)C(N2C=NC=N2)C3=CC=C(C=C3)C#N

InChI

InChIKey=HPJKCIUCZWXJDR-UHFFFAOYSA-N

InChI=1S/C17H11N5/c18-9-13-1-5-15(6-2-13)17(22-12-20-11-21-22)16-7-3-14(10-19)4-8-16/h1-8,11-12,17H

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020726s027lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=17912632

Letrozole (trade name Femara), a nonsteroidal aromatase inhibitor. Femara is indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. Also is indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women, who have received 5 years of adjuvant tamoxifen therapy. Femara has to be used for first-line treatment of postmenopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Treatment of breast cancer thought to be hormonally responsive (i.e., estrogen and/or progesterone receptor positive or receptor unknown) has included a variety of efforts to decrease estrogen levels (ovariectomy, adrenalectomy, hypophysectomy) or inhibit estrogen effects (antiestrogens and progestational agents). These interventions lead to decreased tumor mass or delayed progression of tumor growth in some women. 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. Letrozole inhibits the conversion of androgens to estrogens. Letrozole selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis. Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues. Treatment of women with letrozole significantly lowers serum estrone, estradiol and estrone sulfate and has not been shown to significantly affect adrenal corticosteroid synthesis, aldosterone synthesis, or synthesis of thyroid hormones. Letrozole is rapidly and completely absorbed from the gastrointestinal tract and absorption is not affected by food. Metabolism to a pharmacologically inactive carbinol metabolite (4,4'¬ methanol-bisbenzonitrile) and renal excretion of the glucuronide conjugate of this metabolite is the major pathway of letrozole clearance. In human microsomes with specific CYP isozyme activity, CYP3A4 metabolized letrozole to the carbinol metabolite while CYP2A6 formed both this metabolite and its ketone analog. In human liver microsomes, letrozole strongly inhibited CYP2A6 and moderately inhibited CYP2C19. The most common side effects are sweating, hot flashes, arthralgia (joint pain), and fatigue

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 19A1 37 Target ID: CHEMBL1978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15026471	Inhibitor 8146		7.27 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 426 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020726s027lbl.pdf	Primary		Approved 8307	FEMARA Approved Use 1.1 Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. 1.2 Extended Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women, who have received 5 years of adjuvant tamoxifen therapy. The effectiveness of letrozole tablets in extended adjuvant treatment of early breast cancer is based on an analysis of disease-free survival in patients treated with letrozole tablets for a median of 60 months [see Clinical Studies (14.2, 14.3) Launch Date 8.6978881E11

C_max

Value	Dose	Co-administered	Analyte	Population
128 nM REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		LETROZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4.26 μM × h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		LETROZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
41.9 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		LETROZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg 1 times / day single, oral Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: single Dose: 30 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf https://pubmed.ncbi.nlm.nih.gov/8345034/	healthy, Mean age 28.4 years n = 3 Health Status: healthy Age Group: Mean age 28.4 years Sex: M Population Size: 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf https://pubmed.ncbi.nlm.nih.gov/8345034/	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf https://pubmed.ncbi.nlm.nih.gov/8345034/
2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10	unhealthy, Mean age 63.6 years n = 174 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 63.6 years Sex: F Population Size: 174 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10	Other AEs: Bilirubin abnormal, Aspartate aminotransferase abnormal... Other AEs: Bilirubin abnormal (grade 3, 5%) Aspartate aminotransferase abnormal (grade 3, 3%) ALT increased (grade 3, 3%) Gamma-glutamyltransferase increased (grade 3, 6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10
2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40	unhealthy, Mean age 66 years n = 185 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 66 years Sex: F Population Size: 185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40	Disc. AE: Hypercalcemia, Cerebrovascular accident... Other AEs: Bilirubin abnormal, Aspartate aminotransferase abnormal... AEs leading to discontinuation/dose reduction: Hypercalcemia Cerebrovascular accident Other AEs: Bilirubin abnormal (grade 3, 3%) Aspartate aminotransferase abnormal (grade 3, 4%) ALT increased (grade 3, 1%) Gamma-glutamyltransferase increased (grade 3, 9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40
10 mg 1 times / day multiple, oral Highest studied dose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf https://pubmed.ncbi.nlm.nih.gov/11510690/	unhealthy, Mean age 71.6 years n = 12 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 71.6 years Sex: F Population Size: 12 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf https://pubmed.ncbi.nlm.nih.gov/11510690/	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf https://pubmed.ncbi.nlm.nih.gov/11510690/
62.5 mg 1 times / day single, oral Studied dose Dose: 62.5 mg, 1 times / day Route: oral Route: single Dose: 62.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf	unknown n = 1 Health Status: unknown Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020726s035lbl.pdf

AEs

AE	Significance	Dose	Population
ALT increased	grade 3, 3%	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10	unhealthy, Mean age 63.6 years n = 174 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 63.6 years Sex: F Population Size: 174 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10
Aspartate aminotransferase abnormal	grade 3, 3%	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10	unhealthy, Mean age 63.6 years n = 174 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 63.6 years Sex: F Population Size: 174 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10
Bilirubin abnormal	grade 3, 5%	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10	unhealthy, Mean age 63.6 years n = 174 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 63.6 years Sex: F Population Size: 174 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10
Gamma-glutamyltransferase increased	grade 3, 6%	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10	unhealthy, Mean age 63.6 years n = 174 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 63.6 years Sex: F Population Size: 174 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P4.PDF Page: 20726_FEMARA%202.5MG_MEDR_P4.PDF - p.10
Cerebrovascular accident	Disc. AE	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40	unhealthy, Mean age 66 years n = 185 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 66 years Sex: F Population Size: 185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40
Hypercalcemia	Disc. AE	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40	unhealthy, Mean age 66 years n = 185 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 66 years Sex: F Population Size: 185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40
ALT increased	grade 3, 1%	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40	unhealthy, Mean age 66 years n = 185 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 66 years Sex: F Population Size: 185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40
Bilirubin abnormal	grade 3, 3%	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40	unhealthy, Mean age 66 years n = 185 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 66 years Sex: F Population Size: 185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40
Aspartate aminotransferase abnormal	grade 3, 4%	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40	unhealthy, Mean age 66 years n = 185 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 66 years Sex: F Population Size: 185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40
Gamma-glutamyltransferase increased	grade 3, 9%	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40	unhealthy, Mean age 66 years n = 185 Health Status: unhealthy Condition: breast cancer Age Group: Mean age 66 years Sex: F Population Size: 185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_MEDR_P5.PDF Page: 20726_FEMARA%202.5MG_MEDR_P5.PDF - p.40

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670	substrate 985	substrate 1168

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 670 CYP2C19 1410 CYP2B6 770	CYP2A6 510 CYP1A1 344 CYP1A2 1013 CYP1B1 90 CYP2B6 648 CYP2C8 670 CYP2C19 955 CYP2E1 633 CYP3A5 383

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2A6 702	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF#page=4 Page: 4.0	yes [Ki 0.12 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF#page=4 Page: 4.0	yes [Ki 8.5 uM]
CYP2B6 946	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19198839/ Page: -	yes	4,4'-methanol-bisbenzonitrile 1
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19198839/ Page: -	yes	4,4'-methanol-bisbenzonitrile 1

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 344	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP1A2 1013	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP1B1 90	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2B6 648	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2C19 955	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2C8 670	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2C9 985	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2D6 1168	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2E1 633	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP3A5 383	substrate 3264 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2A6 510	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF#page=4 Page: 4.0	yes	yes (co-administration study) Comment: The effect of a 400 mg b.i.d treatment with cimetidine for 7 days on the letrozole pharmacokinetics after a single 2.5-mg dose was investigated in 16 healthy subjects [Protocol 004], A slight but statistically significant decrease in systemic exposure and an increase in Cmax were observed when letrozole was administered together with cimetidine (table below). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF#page=4 Page: 4.0
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF#page=4 Page: 4.0	yes	yes (co-administration study) Comment: The effect of a 400 mg b.i.d treatment with cimetidine for 7 days on the letrozole pharmacokinetics after a single 2.5-mg dose was investigated in 16 healthy subjects [Protocol 004], A slight but statistically significant decrease in systemic exposure and an increase in Cmax were observed when letrozole was administered together with cimetidine (table below). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20726_FEMARA%202.5MG_BIOPHARMR.PDF#page=4 Page: 4.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6413	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6413
ChemicalBook	CB9286355	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9286355
Selleck Chemicals	Letrozole	http://www.selleckchem.com/products/Letrozole.html
ZINC	ZINC000003778874	http://zinc15.docking.org/substances/ZINC000003778874
eMolecules	902038	https://www.emolecules.com/cgi-bin/more?vid=902038

PubMed

Title	Date	PubMed
Treatment of delayed male puberty: efficacy of aromatase inhibition.	2001	11837512
Letrozole as primary medical therapy for locally advanced and large operable breast cancer.	2001 Apr	11510690
Nonsteroidal and steroidal aromatase inhibitors in breast cancer.	2001 Aug	11548977
Endometrial stromal sarcoma: objective response to letrozole.	2001 Aug	11531300
Effect of letrozole on the lipid profile in postmenopausal women with breast cancer.	2001 Aug	11506958
Promising results for Arimidex and Femara.	2001 Dec	12113080
Future use of selective estrogen receptor modulators and aromatase inhibitors.	2001 Dec	11916232
Preliminary data from ongoing adjuvant aromatase inhibitor trials.	2001 Dec	11916231
Neoadjuvant endocrine therapy for breast cancer: medical perspectives.	2001 Dec	11916229
Are differences in the available aromatase inhibitors and inactivators significant?	2001 Dec	11916226
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
Comparative clinical pharmacology and pharmacokinetic interactions of aromatase inhibitors.	2001 Dec	11850211
Aromatase and COX-2 expression in human breast cancers.	2001 Dec	11850206
Aromatase overexpression transgenic mice model: cell type specific expression and use of letrozole to abrogate mammary hyperplasia without affecting normal physiology.	2001 Dec	11850204
False shortening of time to progression in letrozole 2.5-mg dose?	2001 Dec 1	11731525
[Endocrine therapy for advanced or recurrent breast cancer].	2001 Jul	11478139
[Developments of hormonal agents for breast cancer].	2001 Jul	11478137
Huge response to letrozole in inoperable T4 breast cancer: a case report.	2001 Jul-Aug	11725620
Role of anti-aromatase agents in postmenopausal advanced breast cancer.	2001 Oct	11710624
Inhibition of P450 aromatase enhances gonadotropin secretion in early and midpubertal boys: evidence for a pituitary site of action of endogenous E.	2001 Oct	11600558
Aromatase inhibitors: treatment of advanced breast cancer.	2001 Oct 1	11579125
Aromatase inhibitors and inactivators in breast cancer.	2001 Oct 20	11668120
Role of hormones in puberty.	2001 Oct 27	11705526
Advances in aromatase inhibition: clinical efficacy and tolerability in the treatment of breast cancer.	2001 Sep	11555572
Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial.	2001 Sep 15	11559718
Use of ErbB-1 and ErbB-2 to select endocrine therapy for breast cancer: will it play in Peoria?	2001 Sep 15	11559715
Sex reversal and aromatase in the European pond turtle: treatment with letrozole after the thermosensitive period for sex determination.	2001 Sep 15	11555856
Aromatase, aromatase inhibitors, and breast cancer.	2001 Sep-Oct	11550075
Defining the galaxy of gene expression in breast cancer.	2002	12100738
Antiaromatase agents: evolving role in adjuvant therapy.	2002 Apr	12020394
Short-term effects of anastrozole treatment on insulin-like growth factor system in postmenopausal advanced breast cancer patients.	2002 Apr	11983488
[CGS 20267 (Letrozole), a new aromatase inhibitor: early phase II study for postmenopausal women with advanced breast cancer].	2002 Apr	11977539
[Superiority of letrozole compared with tamoxifen as first line therapy of postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group].	2002 Feb	11942036
Current status and future innovations of hormonal agents, chemotherapy and investigational agents in endometrial cancer.	2002 Feb	11801879
Superior efficacy of letrozole versus tamoxifen as first-line therapy.	2002 Feb 1	11821477
Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study.	2002 Feb 1	11821457
Role of low levels of endogenous estrogen in regulation of bone resorption in late postmenopausal women.	2002 Jan	11771665
[Growth rate can be manipulated. Estrogen production in pubertal boys can be blocked by an aromatase inhibitor].	2002 Jan 17	11838072
Reproductive changes in male rats treated perinatally with an aromatase inhibitor.	2002 Jan-Feb	11812536
Human ejaculated spermatozoa contain active P450 aromatase.	2002 Jul	12107254
Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention.	2002 Jul	12101108
Endocrine effects of nonsteroidal aromatase inhibitors and their clinical impact.	2002 Jul 1	12089238
Exemestane: a potent irreversible aromatase inactivator and a promising advance in breast cancer treatment.	2002 Jun	12113050
[Antiestrogen therapy in the treatment of breast neoplasms].	2002 Jun	12063440
Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer.	2002 Mar	11895893
Aromatase inhibitors in breast cancer.	2002 Mar	11854020
Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer.	2002 Mar 15	11896093
[CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study in postmenopausal women with advanced or recurrent breast cancer (no. 2)--evaluation of efficacy and safety at the recommended clinical dose CGS20267 Study Group].	2002 May	12040678
[CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study for postmenopausal women with advanced or recurrent breast cancer (no. 1)--investigation of recommended clinical dose CGS20267 Study Group].	2002 May	12040677

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of Femara (letrozole) is one 2.5 mg tablet administered once a day, without regard to meals.

Route of Administration: Oral

In Vitro Use Guide

After treatment of cells with letrozole (10 nM) for 24 and 48 h, significant inhibition of matrix metalloproteinases (MMP) levels was obtained. Furthermore, concurrent treatment of MCF-7, human epithelial breast cancer cells with 17-beta-estradiol in the presence of letrozole significantly suppressed the estradiol-induced stimulation of MMP levels. Letrozole is a potent in vitro inhibitor of cell proliferation and of type IV collagenases expressed by estrogen receptor (ER)-positive MCF-7 cells and may be of value for suppressing breast tumor growth and invasiveness.

Name

Type

Language

LETROZOLE

Official Name

English

CGS 20267

Code

English

4,4'-(1H-1,2,4-TRIAZOL-1-YLMETHYLENE)DIBENZONITRILE

Systematic Name

English

LETROZOLE [ORANGE BOOK]

Common Name

English

LETROZOLE [USP MONOGRAPH]

Common Name

English

LETROZOLE [USAN]

Common Name

English

FEMARA

Brand Name

English

CGS-20267

Code

English

LETROZOLE COMPONENT OF KISQALI FEMARA CO-PACK

Brand Name

English

KISQALI FEMARA CO-PACK COMPONENT LETROZOLE

Brand Name

English

LETROZOLE [MART.]

Common Name

English

LETROZOLE [USP-RS]

Common Name

English

LETROZOLE [MI]

Common Name

English

LETROZOLE [JAN]

Common Name

English

LETROZOLE [EP IMPURITY]

Common Name

English

LETROZOLE [EP MONOGRAPH]

Common Name

English

Letrozole [WHO-DD]

Common Name

English

BENZONITRILE, 4,4'-(1H-1,2,4-TRIAZOL-1-YLMETHYLENE)BIS-

Systematic Name

English

NSC-759652

Code

English

letrozole [INN]

Common Name

English

LETROZOLE [HSDB]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548381