Identification

Name
Letrozole
Accession Number
DB01006  (APRD01066)
Type
Small Molecule
Groups
Approved, Investigational
Description

Letrozole (INN, trade name Femara®) is an oral non-steroidal aromatase inhibitor that has been introduced for the adjuvant treatment of hormonally-responsive breast cancer

Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Letrozole blocks production of estrogens in this way by competitive, reversible binding to the heme of its cytochrome P450 unit. The action is specific, and letrozole does not reduce production of mineralo- or corticosteroids. In contrast, the antiestrogenic action of tamoxifen, the major medical therapy prior to the arrival of aromatase inhibitors, is due to its interfering with the estrogen receptor, rather than inhibiting estrogen production. Letrozole is approved by the United States Food and Drug Administration (FDA) for the treatment of local or metastatic breast cancer that is hormone receptor positive or has an unknown receptor status in postmenopausal women. Side effects include signs and symptoms of hypoestrogenism. There is concern that long term use may lead to osteoporosis, which is why prescriptions of Letrozole are often accompanied by prescriptions of osteoporosis-fighting medication such as Fosamax. Letrozole has shown to reduce estrogen levels by 98 percent while raising testosterone levels. The anti-estrogen action of letrozole is preferred by athletes and bodybuilders for use during a steroid cycle to reduce bloating due to excess water retention and prevent the formation of gynecomastia related breast tissue that is a side effect of some anabolic steroids. Usage above 2.5 mg/day is known to potentially temporarily kill sex drive. Above 5mg/day for extended periods may cause kidney problems.

Letrozole has also been shown to delay the fusing of the growth plates in adolescents. This may boost the effectiveness of growth hormone, and thus Letrozole is used to treat adolescents and children with short stature.

Structure
Thumb
Synonyms
  • Letrozol
External IDs
CGS 20267 / CGS-20267
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Co LetrozoleTablet2.5 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
FemaraTablet, film coated2.5 mg/1OralNovartis1997-07-31Not applicableUs
FemaraTablet, film coated2.5 mg/1OralPhysicians Total Care, Inc.2005-02-10Not applicableUs
Femara 2.5mgTablet2.5 mgOralNovartis1997-09-02Not applicableCanada
LetrozoleTablet2.5 mgOralPro Doc Limitee2013-02-14Not applicableCanada
LetrozoleTablet2.5 mgOralMeliapharm Inc2011-08-292014-06-25Canada
LetrozoleTablet2.5 mgOralActavis Pharma Company2010-04-28Not applicableCanada
LetrozoleTablet2.5 mgOralTeva2010-04-282013-12-10Canada
Letrozole SunTablet2.5 mgOralTaro Pharmaceuticals, Inc.Not applicableNot applicableCanada
Letrozole TabletsTablet2.5 mgOralFresenius KabiNot applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-letrozole Tablets USPTablet2.5 mgOralAccel Pharma IncNot applicableNot applicableCanada
Ach-letrozoleTablet2.5 mgOralAccord Healthcare Limited2010-05-03Not applicableCanada
Ag-letrozoleTablet2.5 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Apo-letrozoleTablet2.5 mgOralApotex Corporation2012-06-11Not applicableCanada
Auro-letrozoleTablet2.5 mgOralAuro Pharma Inc2013-06-12Not applicableCanada
Bio-letrozoleTablet2.5 mgOralBiomed Pharma2013-02-12Not applicableCanada
Ccp-letrozoleTablet2.5 mgOralCellchem Pharmaceuticals Inc.2017-07-24Not applicableCanada
Dom-letrozoleTablet2.5 mgOralDominion PharmacalNot applicableNot applicableCanada
Ipg-letrozoleTablet2.5 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Jamp-letrozoleTablet2.5 mgOralJamp Pharma Corporation2011-09-30Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Kisqali Femara Co-packLetrozole (2.5 mg/1) + Ribociclib (200 mg/1)KitNovartis2017-05-04Not applicableUs
Kisqali Femara Co-packLetrozole (2.5 mg/1) + Ribociclib (200 mg/1)KitNovartis2017-05-04Not applicableUs
Kisqali Femara Co-packLetrozole (2.5 mg/1) + Ribociclib (200 mg/1)KitNovartis2017-05-04Not applicableUs
Categories
UNII
7LKK855W8I
CAS number
112809-51-5
Weight
Average: 285.3027
Monoisotopic: 285.101445377
Chemical Formula
C17H11N5
InChI Key
HPJKCIUCZWXJDR-UHFFFAOYSA-N
InChI
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
IUPAC Name
4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile
SMILES
N#CC1=CC=C(C=C1)C(N1C=NC=N1)C1=CC=C(C=C1)C#N

Pharmacology

Indication

For the extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy. Also for first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. Also indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

Associated Conditions
Pharmacodynamics

Letrozole is an aromatase inhibitor used in the treatment of breast cancer. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue.

Mechanism of action

Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens. In adult nontumor- and tumorbearing female animals, letrozole is as effective as ovariectomy in reducing uterine weight, elevating serum Leuteinizing hormone (LH), and causing the regression of estrogen-dependent tumors. In contrast to ovariectomy, treatment with letrozole does not lead to an increase in serum (folicile stimulating hormone (FSH). Letrozole selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis.

TargetActionsOrganism
ACytochrome P450 19A1
antagonist
Human
Absorption

Rapidly and completely absorbed. Absorption is not affected by food.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Primarily hepatic via CYP3A4 and CYP2A6. 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. It is metabolized slowly to an inactive metabolite whose glucuronide conjugate is excreted renally, representing the major clearance pathway.

Route of elimination
Not Available
Half life

2 days

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Letrozole.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Letrozole.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Letrozole.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Letrozole.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Letrozole.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Letrozole.
6-Deoxyerythronolide BThe metabolism of Letrozole can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Letrozole.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Letrozole.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Letrozole.
Food Interactions
  • Take without regard to meals. Food slows absorption without decreasing the quantity absorbed.

References

Synthesis Reference

Peter MacDonald, Ettore Bigatti, Pierluigi Rossetto, Zvi Harel, "Process for the preparation of letrozole." U.S. Patent US20070066831, issued March 22, 2007.

US20070066831
General References
  1. Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF: Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5. Epub 2006 May 2. [PubMed:16650422]
External Links
Human Metabolome Database
HMDB0015141
KEGG Drug
D00964
KEGG Compound
C08163
PubChem Compound
3902
PubChem Substance
46504610
ChemSpider
3765
BindingDB
13061
ChEBI
6413
ChEMBL
CHEMBL1444
Therapeutic Targets Database
DAP000626
PharmGKB
PA450196
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Letrozole
ATC Codes
L02BG04 — Letrozole
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (112 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentCancer, Breast1
0CompletedBasic ScienceCancer, Breast1
0RecruitingBasic ScienceCancer of the Ovary1
0RecruitingBasic ScienceCancer, Breast1
0RecruitingBasic ScienceNeoplasms, Brain1
1Active Not RecruitingBasic ScienceTumors, Solid1
1Active Not RecruitingOtherAdvanced Breast Cancer1
1Active Not RecruitingTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Invasive Ductal Breast Carcinoma / Progesterone Receptor-positive Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
1Active Not RecruitingTreatmentHormone Receptor Positive, HER2-negative, Advanced Breast Cancer1
1Active Not RecruitingTreatmentMetastatic or Locally-advanced Unresectable Breast Cancer1
1Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL) / Non-Hodgkin's Lymphoma, Solid Cancers / Solid Cancers1
1CompletedNot AvailableHealthy Volunteers2
1CompletedOtherAdvanced or Metastatic Breast Cancer1
1CompletedPreventionHealthy, no Evidence of Disease / Lobular Breast Carcinoma In Situ1
1CompletedTreatmentCancer, Breast2
1CompletedTreatmentCancer, Breast / Metastatic Breast Cancer, Locally Advanced Breast Cancer1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentMcCune Albright Syndrome / Polyostotic Fibrous Dysplasia / Puberty, Precocious1
1CompletedTreatmentMetastatic Breast Cancer (MBC)1
1Not Yet RecruitingTreatmentAnatomic Stage III Breast Cancer AJCC v8 / Anatomic Stage IIIA Breast Cancer AJCC v8 / Anatomic Stage IIIB Breast Cancer AJCC v8 / Anatomic Stage IIIC Breast Cancer AJCC v8 / Anatomic Stage IV Breast Cancer AJCC v8 / Estrogen Receptor Positive / HER2/Neu Negative / Invasive Breast Carcinoma / Prognostic Stage III Breast Cancer AJCC v8 / Prognostic Stage IIIA Breast Cancer AJCC v8 / Prognostic Stage IIIB Breast Cancer AJCC v8 / Prognostic Stage IIIC Breast Cancer AJCC v8 / Prognostic Stage IV Breast Cancer AJCC v8 / Recurrent Breast Carcinoma1
1Not Yet RecruitingTreatmentCastration Resistant Prostate Cancer (CRPC) / Hormone Receptor Positive Advanced Breast Cancer / Human Epidermal Receptor 2 Negative Advanced Breast Cancer / Metastatic Breast Cancer (MBC)1
1RecruitingOtherHealthy Volunteers1
1RecruitingTreatmentCancer, Advanced / Lung Cancer Non-Small Cell Cancer (NSCLC) / Mesothelioma, Malignant / Metastatic Breast Cancer (MBC) / Metastatic Cancers / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentCancer, Breast4
1RecruitingTreatmentCancer, Breast / Carcinoma, Breast / Malignant Neoplasm of Breast1
1RecruitingTreatmentCancer, Breast / Tumors, Solid2
1RecruitingTreatmentNeoplasms, Breast1
1RecruitingTreatmentNeoplasms / Neoplasms, Breast1
1TerminatedTreatmentCancer, Breast2
1TerminatedTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer1
1WithdrawnTreatmentSymptomatic or Large Uterine Fibroids1
1, 2Active Not RecruitingTreatmentCancer, Breast1
1, 2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
1, 2CompletedNot AvailableCancer, Breast1
1, 2CompletedTreatmentAndrogen Deficiency / BMI >30 kg/m2 / Insulin Resistance / Metabolic Diseases / Type 2 Diabetes Mellitus1
1, 2CompletedTreatmentCancer, Breast1
1, 2CompletedTreatmentOvarian Stimulation1
1, 2RecruitingTreatmentAdvanced Breast Cancer1
1, 2RecruitingTreatmentCancer, Breast3
1, 2RecruitingTreatmentEstrogen Receptor Positive / HER2/Neu Negative / Invasive Breast Carcinoma / Multifocal Breast Carcinoma / One to five years postmenopausal / Progesterone Receptor Positive / Stage I Breast Carcinoma / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage II Breast Cancer / Stage IIA Breast Cancer / Stage IIB Breast Cancer / Stage III Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
1, 2TerminatedTreatmentCancer, Breast1
2Active Not RecruitingBasic ScienceCancer, Breast1
2Active Not RecruitingTreatmentAdvanced, Persistent, or Recurrent Endometrial Cancer1
2Active Not RecruitingTreatmentAnatomic Stage IV Breast Cancer AJCC v8 / Cancer, Breast / Estrogen Receptor Positive / KIT Positive / One to five years postmenopausal / PDGFR Positive / Progesterone Receptor Positive / Prognostic Stage IV Breast Cancer AJCC v81
2Active Not RecruitingTreatmentBreast Cancer Invasive Nos1
2Active Not RecruitingTreatmentCancer of the Breast / Cancer, Breast / Neoplasms, Breast1
2Active Not RecruitingTreatmentCancer, Breast6
2Active Not RecruitingTreatmentCancer, Breast / Carcinoma, Breast / Tumors, Breast1
2Active Not RecruitingTreatmentEndometrial Cancers2
2Active Not RecruitingTreatmentEstrogen Receptor Positive / One to five years postmenopausal / RB1 Positive / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Recurrent Uterine Corpus Carcinoma1
2Active Not RecruitingTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Recurrent Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
2Active Not RecruitingTreatmentHormone Receptor Positive Breast Cancer1
2Active Not RecruitingTreatmentMalignant Ovarian Mixed Epithelial Tumor / Ovarian Endometrioid Adenocarcinoma / Ovarian Seromucinous Carcinoma / Ovarian Serous Cystadenocarcinoma / Ovarian Serous Surface Papillary Adenocarcinoma / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Ovarian Germ Cell Tumor / Recurrent Primary Peritoneal Carcinoma / Undifferentiated Ovarian Carcinoma1
2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)2
2Active Not RecruitingTreatmentNeoadjuvant Operable Breast Cancer1
2Active Not RecruitingTreatmentNeoplasms, Breast2
2Active Not RecruitingTreatmentNeoplasms / Neoplasms, Breast1
2CompletedDiagnosticCancer, Breast1
2CompletedPreventionCancer, Breast5
2CompletedSupportive CareDuctal Carcinoma In Situ / Estrogen Receptor-Positive Breast Cancer / Progesterone Receptor-positive Breast Cancer / Stage I Breast Carcinoma / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
2CompletedSupportive CareArthralgia/joint pain / Musculoskeletal Complications / Pain / Recurrent Breast Cancer / Stage I Breast Carcinoma / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
2CompletedTreatmentCancer, Breast16
2CompletedTreatmentEndometrial Cancers2
2CompletedTreatmentEstrogen Receptor-negative Breast Cancer / Estrogen Receptor-Positive Breast Cancer / Her2-Positive Breast Cancer / Progesterone Receptor-negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer1
2CompletedTreatmentHighly Endocrine Responsive Operable Breast Cancer1
2CompletedTreatmentLeiomyosarcomas1
2CompletedTreatmentLymphangioleiomyomatosis1
2CompletedTreatmentMetastatic Breast Cancer (MBC)5
2CompletedTreatmentNeoplasms, Breast4
2CompletedTreatmentPostmenopausal Women With Advanced Breast Cancer3
2CompletedTreatmentPregnancy1
2CompletedTreatmentRecurrent and Metastatic Endometrial Cancer1
2CompletedTreatmentSevere and Recurrent Endometriosis1
2Not Yet RecruitingOtherHR+ HER2 Breast Cancer1
2Not Yet RecruitingTreatmentAnatomic Stage IV Breast Cancer AJCC v8 / Estrogen Receptor Positive / HER2/Neu Negative / Metastatic Breast Carcinoma / Metastatic Malignant Neoplasm in the Bone / Progesterone Receptor Positive / Prognostic Stage IV Breast Cancer AJCC v81
2Not Yet RecruitingTreatmentAnovulatory cycle / Polycystic Ovaries Syndrome1
2Not Yet RecruitingTreatmentCancer, Breast1
2Not Yet RecruitingTreatmentCancer, Breast / Estrogen Receptor Positive Tumor / Her2-Positive Breast Cancer1
2Not Yet RecruitingTreatmentEndometrial Cancers1
2Not Yet RecruitingTreatmentLow Grade Endometrial Stromal Sarcoma1
2Not Yet RecruitingTreatmentLow Grade Serous Carcinoma1
2Not Yet RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingPreventionBone destruction / Cancer, Breast1
2RecruitingTreatmentAbortions spontaneous / Missed Abortion1
2RecruitingTreatmentBreast Cancer Invasive Nos / Cancer, Breast2
2RecruitingTreatmentBreast Cancer Metastatic2
2RecruitingTreatmentCancer of the Breast / Cancer, Breast / Carcinoma, Breast1
2RecruitingTreatmentCancer of the Breast / Cancer, Breast / Carcinoma, Breast / Malignant Tumor of Breast1
2RecruitingTreatmentCancer of the Ovary / Endometrial Cancers1
2RecruitingTreatmentCancer, Breast11
2RecruitingTreatmentCancer, Breast / Hormone Receptor Positive Tumor / Human Epidermal Growth Factor 2 Negative Carcinoma of Breast1
2RecruitingTreatmentEarly-Stage Breast Carcinoma / Estrogen Receptor Positive Tumor1
2RecruitingTreatmentEndometrial Cancers1
2RecruitingTreatmentEndometrial Carcinoma / Malignant Neoplasms of Female Genital Organs1
2RecruitingTreatmentEstrogen Receptor Negative / Estrogen Receptor Positive / HER2/Neu Negative / Progesterone Receptor Negative / Progesterone Receptor Positive / Stage IV Breast Cancer / Triple-Negative Breast Carcinoma1
2RecruitingTreatmentEstrogen Receptor Positive / HER2/Neu Negative / One to five years postmenopausal / Recurrent Breast Carcinoma / Stage IV Breast Cancer1
2RecruitingTreatmentEstrogen Receptor-Positive Breast Cancer / HER2/Neu Negative / Stage IV Breast Cancer AJCC v6 and v71
2RecruitingTreatmentMetastatic Breast Cancer (MBC)3
2RecruitingTreatmentNeoplasms, Breast3
2RecruitingTreatmentUterine Cervical Neoplasms1
2TerminatedNot AvailableStage I Breast Carcinoma1
2TerminatedTreatmentAdvanced Breast Cancer (Phase 1b) / Early Breast Cancer (Phase 2)1
2TerminatedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
2TerminatedTreatmentCancer, Breast6
2TerminatedTreatmentCarcinoma, Breast1
2TerminatedTreatmentEndocrine Breast Diseases / Neoplasms Metastasis / Neoplasms, Breast1
2TerminatedTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
2TerminatedTreatmentHormone-sensitive Metastatic Breast Cancer1
2TerminatedTreatmentLeiomyosarcomas / Uterine Neoplasms1
2TerminatedTreatmentMedical Abortion, Complete or Unspecified, Without Complication1
2TerminatedTreatmentNeoplasms, Breast1
2Unknown StatusPreventionCancer, Breast / One to five years postmenopausal1
2Unknown StatusTreatmentCancer, Breast1
2Unknown StatusTreatmentCancer, Breast / Hormone-Sensitive Breast Cancer1
2WithdrawnTreatmentBreast Cancer Stage II / Breast Cancer Stage III / Cancer, Breast1
2WithdrawnTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
2WithdrawnTreatmentCancer, Breast1
2, 3Active Not RecruitingNot AvailableHealthy Volunteers / Idiopathic Hypogonadotropic Hypogonadism / Olfacto genital dysplasia1
2, 3Active Not RecruitingTreatmentInfertilities1
2, 3Active Not RecruitingTreatmentLow Grade Ovarian Serous Adenocarcinoma / Micropapillary Serous Carcinoma / Ovarian Serous Adenocarcinoma / Primary Peritoneal Serous Adenocarcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2, 3Active Not RecruitingTreatmentUterine Cancers1
2, 3CompletedOtherPolycystic Ovaries Syndrome1
2, 3CompletedTreatmentAbortions spontaneous1
2, 3CompletedTreatmentCancer, Breast1
2, 3CompletedTreatmentComplete Miscarriage1
2, 3CompletedTreatmentConstitutional Delay of Growth and Puberty1
2, 3CompletedTreatmentMetastatic Breast Cancer (MBC)1
2, 3Not Yet RecruitingTreatmentCancer treatment / Cancer, Breast / Endocrine Breast Diseases1
2, 3RecruitingTreatmentInfertilities1
2, 3RecruitingTreatmentInflammatory carcinoma of the breast / Invasive Ductal Breast Carcinoma / Mucinous Breast Cancer / Tubular Breast Carcinoma1
3Active Not RecruitingPreventionCancer, Breast1
3Active Not RecruitingPreventionBrca1 Mutation Carrier / Brca2 Mutation Carrier / Cancer, Breast / Hereditary Breast/Ovarian Cancer (brca1, brca2)1
3Active Not RecruitingTreatmentAdvanced Metastatic Breast Cancer / Advanced, Metastatic Breast Cancer1
3Active Not RecruitingTreatmentAdvanced, Metastatic Breast Cancer1
3Active Not RecruitingTreatmentBreast Adenocarcinoma / Estrogen Receptor and/or Progesterone Receptor Positive / HER2/Neu Negative / Stage IA Breast Cancer / Stage IA Breast Cancer AJCC v7 / Stage IB Breast Cancer / Stage IB Breast Cancer AJCC v7 / Stage IIA Breast Cancer / Stage IIA Breast Cancer AJCC v6 and v7 / Stage IIB Breast Cancer / Stage IIB Breast Cancer AJCC v6 and v7 / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v71
3Active Not RecruitingTreatmentBreast Cancer Metastatic1
3Active Not RecruitingTreatmentCancer, Breast9
3Active Not RecruitingTreatmentDuctal Breast Carcinoma In Situ / Estrogen Receptor and/or Progesterone Receptor Positive / HER2/Neu Negative / Invasive Breast Carcinoma / Multicentric Breast Carcinoma / Multifocal Breast Carcinoma / Synchronous Bilateral Breast Carcinoma1
3Active Not RecruitingTreatmentEstrogen Receptor Positive / Progesterone Receptor Positive / Recurrent Breast Carcinoma / Stage IIIB Breast Cancer / Stage IV Breast Cancer1
3Active Not RecruitingTreatmentNeoplasms, Breast2
3CompletedPreventionBone destruction / Neoplasms, Breast1
3CompletedSupportive CareBone destruction / Cancer, Breast1
3CompletedTreatmentAzoospermia, Nonobstructive / Oligozoospermia1
3CompletedTreatmentBMI >30 kg/m2 / Hypogonadotrophic Hypogonadism1
3CompletedTreatmentBone Loss / Cancer, Breast1
3CompletedTreatmentCancer, Breast9
3CompletedTreatmentHormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women1
3CompletedTreatmentIdiopathic Short Stature (ISS)1
3CompletedTreatmentInfertilities2
3CompletedTreatmentMalignant Neoplasm of Female Breast1
3CompletedTreatmentNeoplasms, Breast1
3CompletedTreatmentNeoplasms, Breast / Neoplasms, Hormone-Dependent1
3CompletedTreatmentPolycystic Ovarian Syndrome1
3CompletedTreatmentPolycystic Ovaries Syndrome / Pregnancy1
3CompletedTreatmentPregnancy / Unexplained Infertility1
3CompletedTreatmentUnexplained Infertility1
3CompletedTreatmentBone destruction / One to five years postmenopausal1
3Not Yet RecruitingPreventionOvarian Hyperstimulation Syndrome1
3Not Yet RecruitingTreatmentPolycystic Ovaries Syndrome1
3RecruitingOtherCancer, Breast1
3RecruitingTreatmentAdvanced Breast Cancer (Female) / Advanced Breast Cancer Female1
3RecruitingTreatmentAdvanced Metastatic Breast Cancer1
3RecruitingTreatmentBreast Neoplasm Female1
3RecruitingTreatmentCancer, Breast7
3RecruitingTreatmentEstrogen Receptor Positive Breast Cancer / HER-2 Positive Breast Cancer1
3RecruitingTreatmentInfertilities3
3RecruitingTreatmentInfertility, Female1
3RecruitingTreatmentMetastatic Breast Cancer (MBC)1
3RecruitingTreatmentNeoadjuvant Therapy1
3RecruitingTreatmentPolycystic Ovaries Syndrome1
3RecruitingTreatmentSubfertility1
3TerminatedTreatmentNeoplasms, Breast / Neoplasms, Hormone-Dependent2
3TerminatedTreatmentOperable Breast Neoplasms1
3Unknown StatusTreatmentCancer, Breast3
3WithdrawnTreatmentCancer, Breast1
4Active Not RecruitingPreventionFertility / Neoplasms, Breast1
4Active Not RecruitingTreatmentInfertilities / Polycystic Ovaries Syndrome1
4Active Not RecruitingTreatmentLeiomyomas / Uterine Leiomyomas1
4CompletedBasic ScienceFertility1
4CompletedDiagnosticESTROGENS/RIFAMPIN [VA Drug Interaction] / Ovarian Cysts / Ovulatory Dysfunction1
4CompletedPreventionCancer, Breast1
4CompletedPreventionOvarian Hyperstimulation Syndrome1
4CompletedTreatmentCancer, Breast4
4CompletedTreatmentHormono-depending Adjuvant Breast Cancer1
4CompletedTreatmentInfertilities1
4CompletedTreatmentInfertilities / Polycystic Ovarian Syndrome1
4CompletedTreatmentInfertility Indicated for ICSI1
4CompletedTreatmentLocally Advanced Breast Cancer (LABC)1
4CompletedTreatmentLocally Advanced Metastatic Breast Cancer / Locally Advanced or Metastatic Breast Cancer / Metastatic Breast Cancer (MBC) / Postmenopausal Women1
4Not Yet RecruitingTreatmentHER2/Neu Negative / Invasive Breast Carcinoma / One to five years postmenopausal / Stage 0 Breast Cancer / Stage IA Breast Cancer1
4RecruitingHealth Services ResearchBMI >30 kg/m21
4RecruitingTreatmentAnovulatory cycle1
4RecruitingTreatmentCancer, Breast1
4RecruitingTreatmentNeoplasms, Breast1
4RecruitingTreatmentShort Stature1
4TerminatedTreatmentMetastatic Breast Cancer (MBC)2
4TerminatedTreatmentNeoplasms, Breast1
4Unknown StatusTreatmentCancer, Breast1
4Unknown StatusTreatmentIs to Identify Biomarkers That Could Predict the Efficacy of an Adjuvant Letrozol Treatment in Postmenopausal Breast Cancer Patients1
4WithdrawnTreatmentInfertilities1
Not AvailableActive Not RecruitingNot AvailableCancer, Breast1
Not AvailableActive Not RecruitingTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
Not AvailableActive Not RecruitingTreatmentNeoplasms, Breast1
Not AvailableCompletedNot AvailableBMI >30 kg/m21
Not AvailableCompletedNot AvailableArthralgia/joint pain / BMI >30 kg/m2 / Cancer, Breast1
Not AvailableCompletedNot AvailableCancer, Breast1
Not AvailableCompletedNot AvailableArthralgia/joint pain / Cancer, Breast / Pain1
Not AvailableCompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedNot AvailableInfertilities1
Not AvailableCompletedNot AvailableArthralgia/joint pain1
Not AvailableCompletedBasic ScienceCancer, Breast1
Not AvailableCompletedHealth Services ResearchOvarian Follicle1
Not AvailableCompletedHealth Services ResearchPolycystic Ovaries Syndrome1
Not AvailableCompletedOtherInfertilities1
Not AvailableCompletedPreventionBone destruction / Cancer, Breast1
Not AvailableCompletedTreatmentCancer, Breast1
Not AvailableCompletedTreatmentEndometrial Carcinoma1
Not AvailableCompletedTreatmentEndometriosis1
Not AvailableCompletedTreatmentInfertilities1
Not AvailableCompletedTreatmentInfertility Poly Cystic Ovary1
Not AvailableCompletedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
Not AvailableCompletedTreatmentPolycystic Ovaries Syndrome3
Not AvailableCompletedTreatmentPoor Responders1
Not AvailableEnrolling by InvitationNot AvailableCancer, Breast1
Not AvailableNo Longer AvailableNot AvailableAdvanced Breast Cancer (Female)1
Not AvailableNot Yet RecruitingTreatmentInduction of Abortion1
Not AvailableNot Yet RecruitingTreatmentInfertilities1
Not AvailableNot Yet RecruitingTreatmentInfertilities / Intrauterine Insemination1
Not AvailableNot Yet RecruitingTreatmentInfertilities / Polycystic Ovaries Syndrome1
Not AvailableRecruitingBasic ScienceCancer, Breast1
Not AvailableRecruitingBasic ScienceNeoplasms1
Not AvailableRecruitingTreatmentCancer, Breast1
Not AvailableRecruitingTreatmentCancer, Breast / Infertilities1
Not AvailableRecruitingTreatmentFemale Infertility Due to Nonimplantation of Ovum1
Not AvailableRecruitingTreatmentNeoplasms Metastasis / Neoplasms, Breast1
Not AvailableRecruitingTreatmentPolycystic Ovarian Syndrome / Subfertility1
Not AvailableUnknown StatusNot AvailableArterial hypoxia / Cancer, Breast1
Not AvailableUnknown StatusTreatmentComplete Abortion1
Not AvailableUnknown StatusTreatmentInfertilities2
Not AvailableUnknown StatusTreatmentPolycystic Ovarian Syndrome1
Not AvailableUnknown StatusTreatmentPolycystic Ovaries Syndrome2

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
  • Mylan pharmaceuticals inc
Packagers
  • Kaiser Foundation Hospital
  • Novartis AG
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
TabletOral2.5 mg
Kit
TabletOral2.5 mg/1
Tablet, coatedOral2.5 mg/1
Tablet, film coatedOral2.5 mg/1
Prices
Unit descriptionCostUnit
Femara 2.5 mg tablet16.87USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4978672No1994-06-032011-06-03Us
US8685980No2010-05-252030-05-25Us
US9193732No2011-11-092031-11-09Us
US8415355No2011-02-192031-02-19Us
US8324225No2008-06-172028-06-17Us
US9416136No2009-08-202029-08-20Us
US8962630No2009-12-092029-12-09Us
US9868739No2011-11-092031-11-09Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)184-185 °CNot Available
logP2.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0799 mg/mLALOGPS
logP1.86ALOGPS
logP2.94ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)2.17ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area78.29 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity94.47 m3·mol-1ChemAxon
Polarizability29.59 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9965
Blood Brain Barrier+0.9737
Caco-2 permeable+0.6347
P-glycoprotein substrateNon-substrate0.8391
P-glycoprotein inhibitor INon-inhibitor0.8087
P-glycoprotein inhibitor IINon-inhibitor0.9147
Renal organic cation transporterNon-inhibitor0.5908
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6843
CYP450 1A2 substrateNon-inhibitor0.8374
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorInhibitor0.8993
CYP450 3A4 inhibitorInhibitor0.6451
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7027
Ames testNon AMES toxic0.6371
CarcinogenicityNon-carcinogens0.8926
BiodegradationNot ready biodegradable0.9864
Rat acute toxicity1.9916 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9261
hERG inhibition (predictor II)Non-inhibitor0.8817
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-0090000000-0fbd577a32ff572f7368
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-0190000000-dfcab9af789387521571
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0006-0390000000-dbc68fd6017abe6e8adc
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00kf-0490000000-c3fc389848a06a012234
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014l-0690000000-38ba597054b02b136ab6
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00kf-1980000000-13a8827cbc5c1b36a14f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00kf-3940000000-e01d63313ef1cfa7477a
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-9410000000-83b93aed0756bd41adaf
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-9100000000-d1757f8c218d5dcc4809
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0090000000-791121bd513899b7dfc0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0090000000-eb3996846ea4f036ccca
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0390000000-a57ce4cfb24ba743c54b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0950000000-303d99867511fe3a013b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0930000000-77e720374927be5113ef
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0920000000-4a93d8e76eb7d0d59481
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03du-0910000000-8ad9f37884e8686ef7ba
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03dr-2900000000-2274a3adb5e486f57001
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03dr-6900000000-74d56231c43250bc65ca
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0490000000-7868daa9f0ec9ebda34a

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Benzonitriles / Triazoles / Heteroaromatic compounds / Nitriles / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Diphenylmethane / Benzonitrile / Heteroaromatic compound / 1,2,4-triazole / Azole / Azacycle / Organoheterocyclic compound / Nitrile / Carbonitrile / Organic nitrogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nitrile, triazoles (CHEBI:6413)

Targets

Details
1. Cytochrome P450 19A1
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Ebert AD, Bartley J, David M, Schweppe KW: [Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis]. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51. [PubMed:14505258]
  3. Long BJ, Jelovac D, Handratta V, Thiantanawat A, MacPherson N, Ragaz J, Goloubeva OG, Brodie AM: Therapeutic strategies using the aromatase inhibitor letrozole and tamoxifen in a breast cancer model. J Natl Cancer Inst. 2004 Mar 17;96(6):456-65. [PubMed:15026471]
  4. Murphy MJ Jr: Molecular Action and Clinical Relevance of Aromatase Inhibitors. Oncologist. 1998;3(2):129-130. [PubMed:10388095]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Jeong S, Woo MM, Flockhart DA, Desta Z: Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4'-methanol-bisbenzonitrile in vitro. Cancer Chemother Pharmacol. 2009 Oct;64(5):867-75. doi: 10.1007/s00280-009-0935-7. Epub 2009 Feb 7. [PubMed:19198839]
  3. Raunio H, Rautio A, Gullsten H, Pelkonen O: Polymorphisms of CYP2A6 and its practical consequences. Br J Clin Pharmacol. 2001 Oct;52(4):357-63. [PubMed:11678779]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:33