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 39 Target ID: CHEMBL1978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15026471	Inhibitor 8297		7.27 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020726s027lbl.pdf	Primary		Approved 8429	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 1997

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 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 707 CYP2C19 1478 CYP2B6 810	CYP2A6 543 CYP1A1 349 CYP1A2 1054 CYP1B1 92 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667 CYP3A5 395

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2A6 739	inhibitor 3277 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 1553	inhibitor 3277 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 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19198839/ Page: -	yes	4,4'-methanol-bisbenzonitrile 1
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19198839/ Page: -	yes	4,4'-methanol-bisbenzonitrile 1

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 349	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP1A2 1054	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP1B1 92	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2B6 664	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2C19 991	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2C8 693	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2C9 1037	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2D6 1217	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2E1 667	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP3A5 395	substrate 3367 Sources: https://www.tandfonline.com/doi/pdf/10.3109/00498250903171395?needAccess=true Page: -	no
CYP2A6 543	substrate 3367 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 1737	substrate 3367 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
Aromatase inhibitors.	2001	11900315
Treatment of delayed male puberty: efficacy of aromatase inhibition.	2001	11837512
Aromatase and aromatase inhibitors.	2001	11791126
Third-generation aromatase inhibitors in the treatment of advanced breast cancer.	2001	11791122
[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects].	2001	11785098
Promising results for Arimidex and Femara.	2001 Dec	12113080
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
17alpha-methyl testosterone is a competitive inhibitor of aromatase activity in Jar choriocarcinoma cells and macrophage-like THP-1 cells in culture.	2001 Dec	11850230
Where do selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) now fit into breast cancer treatment algorithms?	2001 Dec	11850229
Adjuvant trials of aromatase inhibitors: determining the future landscape of adjuvant endocrine therapy.	2001 Dec	11850217
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
Local endocrine effects of aromatase inhibitors within the breast.	2001 Dec	11850212
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
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	11742322
False shortening of time to progression in letrozole 2.5-mg dose?	2001 Dec 1	11731525
Letrozole in second-line therapy of advanced breast cancer: more questions than answers.	2001 Dec 1	11731524
New breast cancer drug.	2001 Dec 24	11793594
Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femara) in breast cancer patients.	2001 Jul	11745921
Huge response to letrozole in inoperable T4 breast cancer: a case report.	2001 Jul-Aug	11725620
Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still achievable?	2001 Nov	11822752
Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study.	2001 Nov	11822750
Pre-operative endocrine therapy for postmenopausal women: when and why?	2001 Nov	11822746
Defining the galaxy of gene expression in breast cancer.	2002	12100738
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
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
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
[Aromatase inhibitors of the 3rd generation. What can the "pill against breast cancer" really do?].	2002 Jan 31	11883037
Reproductive changes in male rats treated perinatally with an aromatase inhibitor.	2002 Jan-Feb	11812536
Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue.	2002 Jul	12107266
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
Exemestane: a potent irreversible aromatase inactivator and a promising advance in breast cancer treatment.	2002 Jun	12113050
Letrozole for the management of breast cancer.	2002 Jun	12113048
Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer.	2002 Mar	11895893
The role of sex steroids in the regulation of insulin sensitivity and serum lipid concentrations during male puberty: a prospective study with a P450-aromatase inhibitor.	2002 Mar	11888840
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
Letrozole in the treatment of breast cancer.	2002 May	11996638

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