Identification

Name
Letrozole
Accession Number
DB01006
Description

Letrozole, or CGS 20267, is an oral non-steroidal type II aromatase inhibitor first described in the literature in 1990.1,5,8,9 It is a third generation aromatase inhibitor like exemestane and anastrozole, meaning it does not significantly affect cortisol, aldosterone, and thyroxine.2

Letrozole was granted FDA approval on 25 July 1997.8

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 285.3027
Monoisotopic: 285.101445377
Chemical Formula
C17H11N5
Synonyms
  • Letrozol
  • Letrozole
External IDs
  • CGS 20267
  • CGS-20267

Pharmacology

Indication

Letrozole is indicated to treat postmenopausal women with hormone receptor (HR) positive early breast cancer, postmenopausal women with early breast cancer who have periviously been treated with tamoxifen, and postmenopausal women with HR+ or unknown advanced breast cancer.8 Letrozole, given with ribociclib, is indicated to treat pre, peri, and postmenopausal women with HR+ and human epidermal growth factor 2 (HER2) negative advanced or metastatic breast cancer.9

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
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.

Letrozole is a third generation type II aromatase inhibitor used to treat estrogen dependant breast cancers.8 It has a long duration of action as it has a half life of over 42 hours in breast cancer patients.2,4,8 Patients should be counselled regarding the risk of interstitial lung disease, pneumonitis, QT prolongation, elevated transaminase levels, neutropenia, and embryo-fetal toxicity.8

Mechanism of action

Letrozole is a non-steroidal type II aromatase inhibitor.5 It blocks the active site, and therefore the electron transfer chain of CYP19A1.5 This competitive inhibition prevents the conversion of androgens to estrogen.5 This action leads to a reduction in uterine weight and elevated leuteinizing hormone.8 In postmenopausal women, the action of aromatase is responsible for the majority of estrogen production.8 With reduced availability of estrogen, estrogen-dependant tumors regress.8 Third generation aromatase inhibitors do not significantly affect cortisol, aldosterone, and thyroxine levels.2

TargetActionsOrganism
ACytochrome P450 19A1
antagonist
Humans
Absorption

Letrozole is 99.9% orally bioavailable.2 A 2.5mg oral dose reaches a Cmax of 104nmol/L with a Tmax of 8.10h, and an AUC of 7387nmol*h/L.4

Volume of distribution

The volume of distribution of letrozole is 1.87L/kg.2

Protein binding

Letrozole is 60% bound to proteins.2,4 55% is bound to albumin.2

Metabolism

Letrozole is metabolized by CYP2A6 to a ketone analog metabolite, which is further metabolized by CYP3A4 and CYP2A6 to 4,4'-(hydroxymethylene)dibenzonitrile.[A33288] 4,4'-(hydroxymethylene)dibenzonitrile is glucuronidated by UGT2B7.3

Hover over products below to view reaction partners

Route of elimination

Letrozole is 90% eliminated in the urine.8 75% of the dose is recovered as a glucuronide metabolite, 9% is in the form of the ketone and carbinol metabolites, and 6% is recovered in urine as unchanged letrozole.8

Half-life

The terminal elimination half life of letrozole is approximately 42h in healthy volunteers, but longer in breast cancer patients.2,4,8

Clearance

The average clearance after a single dose of letrozole was 1.52L/h and at steady state was 1.20L/h.4

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Overdose data in humans is not readily available, however 1 reported case was not associated with serious adverse reactions.8 Animal studies do not report serious adverse effects with high dose treatment.6 Patients experiencing and overdose should be treated with symptomatic and supportive measures.8

Oral doses over 2000mg/kg were associated with reduced motor activity, ataxia, dyspnea, and death in mice and rats.8

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

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Letrozole can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Letrozole can be increased when combined with Abatacept.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Letrozole.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Letrozole.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Letrozole is combined with Acipimox.
AdalimumabThe metabolism of Letrozole can be increased when combined with Adalimumab.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Letrozole.
Alendronic acidThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Alendronic acid is combined with Letrozole.
AmiodaroneThe metabolism of Letrozole can be decreased when combined with Amiodarone.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Letrozole.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Take with or without food. Food slows absorption without decreasing the quantity absorbed.

Products

Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Co LetrozoleTabletOralCobalt LaboratoriesNot applicableNot applicableCanada flag
FemaraTablet, film coated2.5 mg/1OralNovartis Pharmaceuticals Corporation1997-07-31Not applicableUS flag
FemaraTablet, film coated2.5 mg/1OralPhysicians Total Care, Inc.2005-02-10Not applicableUS flag
Femara 2.5mgTabletOralNovartis1997-09-02Not applicableCanada flag
LetrozoleTablet2.5 mgOralPro Doc Limitee2013-02-14Not applicableCanada flag
LetrozoleTablet2.5 mgOralMeliapharm Inc2011-08-292014-06-25Canada flag
LetrozoleTablet2.5 mgOralSanis Health IncNot applicableNot applicableCanada flag
LetrozoleTablet2.5 mgOralTEVA Canada Limited2010-04-282013-12-10Canada flag
LetrozoleTablet2.5 mgOralActavis Pharma Company2010-04-282018-06-18Canada flag
Letrozole SunTabletOralTaro Pharmaceuticals, Inc.Not applicableNot applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Accel-letrozole Tablets USPTabletOralAccel Pharma IncNot applicableNot applicableCanada flag
Ach-letrozoleTabletOralAccord Healthcare Inc2010-05-03Not applicableCanada flag
Ag-letrozoleTabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Apo-letrozoleTabletOralApotex Corporation2012-06-11Not applicableCanada flag
Auro-letrozoleTabletOralAuro Pharma Inc2013-06-122015-04-24Canada flag
Bio-letrozoleTabletOralBiomed Pharma2013-02-12Not applicableCanada flag
Ccp-letrozoleTabletOralCellchem Pharmaceuticals Inc.2017-07-24Not applicableCanada flag
Dom-letrozoleTabletOralDominion PharmacalNot applicableNot applicableCanada flag
Ipg-letrozoleTabletOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada flag
Jamp-letrozoleTabletOralJamp Pharma Corporation2011-09-30Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Kisqali Femara Co-packLetrozole (2.5 mg/1) + Ribociclib (200 mg/1)OralNovartis Pharmaceuticals Corporation2017-05-04Not applicableUS flag
Kisqali Femara Co-packLetrozole (2.5 mg/1) + Ribociclib (200 mg/1)OralNovartis Pharmaceuticals Corporation2017-05-04Not applicableUS flag
Kisqali Femara Co-packLetrozole (2.5 mg/1) + Ribociclib (200 mg/1)OralNovartis Pharmaceuticals Corporation2017-05-04Not applicableUS flag

Categories

ATC Codes
L02BG04 — Letrozole
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,2,4-triazole / Aromatic heteromonocyclic compound / Azacycle / Azole / Benzonitrile / Carbonitrile / Diphenylmethane / Heteroaromatic compound / Hydrocarbon derivative / Nitrile
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nitrile, triazoles (CHEBI:6413)

Chemical Identifiers

UNII
7LKK855W8I
CAS number
112809-51-5
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

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. Bhatnagar AS, Hausler A, Schieweck K, Lang M, Bowman R: Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor. J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):1021-7. doi: 10.1016/0960-0760(90)90460-3. [PubMed:2149502]
  2. Bhatnagar AS: The discovery and mechanism of action of letrozole. Breast Cancer Res Treat. 2007;105 Suppl 1:7-17. doi: 10.1007/s10549-007-9696-3. Epub 2007 Oct 3. [PubMed:17912633]
  3. Precht JC, Schroth W, Klein K, Brauch H, Krynetskiy E, Schwab M, Murdter TE: The letrozole phase 1 metabolite carbinol as a novel probe drug for UGT2B7. Drug Metab Dispos. 2013 Nov;41(11):1906-13. doi: 10.1124/dmd.113.053405. Epub 2013 Aug 21. [PubMed:23965986]
  4. Pfister CU, Martoni A, Zamagni C, Lelli G, De Braud F, Souppart C, Duval M, Hornberger U: Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femara) in breast cancer patients. Biopharm Drug Dispos. 2001 Jul;22(5):191-7. doi: 10.1002/bdd.273. [PubMed:11745921]
  5. Nabholtz JM: Long-term safety of aromatase inhibitors in the treatment of breast cancer. Ther Clin Risk Manag. 2008 Feb;4(1):189-204. [PubMed:18728707]
  6. Schieweck K, Bhatnagar AS, Batzl C, Lang M: Anti-tumor and endocrine effects of non-steroidal aromatase inhibitors on estrogen-dependent rat mammary tumors. J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):633-6. doi: 10.1016/0960-0760(93)90270-7. [PubMed:8476774]
  7. Dave N, Chow LM, Gudelsky GA, LaSance K, Qi X, Desai PB: Preclinical pharmacological evaluation of letrozole as a novel treatment for gliomas. Mol Cancer Ther. 2015 Apr;14(4):857-64. doi: 10.1158/1535-7163.MCT-14-0743. Epub 2015 Feb 18. [PubMed:25695958]
  8. FDA Approved Drug Products: Femara Letrozole Oral Tablets [Link]
  9. FDA Approved Drug Products: Kisquali Femara Co-Pack Letrozole and Ribociclib Succinate Oral Tablets [Link]
Human Metabolome Database
HMDB0015141
KEGG Drug
D00964
KEGG Compound
C08163
PubChem Compound
3902
PubChem Substance
46504610
ChemSpider
3765
BindingDB
13061
RxNav
72965
ChEBI
6413
ChEMBL
CHEMBL1444
ZINC
ZINC000003778874
Therapeutic Targets Database
DAP000626
PharmGKB
PA450196
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Letrozole
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (112 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionFertility / Neoplasms, Breast1
4Active Not RecruitingTreatmentBreast Cancer / Infertility1
4Active Not RecruitingTreatmentInvestigative Techniques / Reproductive Techniques / Reproductive Techniques, Assisted1
4CompletedBasic ScienceFertility1
4CompletedDiagnosticESTROGENS/RIFAMPIN [VA Drug Interaction] / Ovarian Cysts / Ovulatory Dysfunction1
4CompletedPreventionBreast Cancer1
4CompletedPreventionOvarian Hyperstimulation Syndrome1
4CompletedTreatmentBreast Cancer5
4CompletedTreatmentHormono-depending Adjuvant Breast Cancer1
4CompletedTreatmentInfertility1

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
  • Mylan pharmaceuticals inc
Packagers
  • Kaiser Foundation Hospital
  • Novartis AG
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
TabletOral
Tablet, film coatedOral2.5 mg
TabletOral2.5 mg
Tablet, film coated2.5 mg
Tablet, coatedOral2.5 mg
Tablet
TabletOral2.5 mg/1
Tablet, coatedOral2.5 mg/1
Tablet, film coatedOral2.5 mg/1
Tablet, coated2.5 MG
Tablet, film coatedOral
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)Region
US4978672No1990-12-182011-06-03US flag
US8685980No2014-04-012030-05-25US flag
US9193732No2015-11-242031-11-09US flag
US8415355No2013-04-092031-02-19US flag
US8324225No2012-12-042028-06-17US flag
US9416136No2016-08-162029-08-20US flag
US8962630No2015-02-242029-12-09US flag
US9868739No2018-01-162031-11-09US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)184-185 °CFDA Label
logP2.5Dave N, et al. 2015
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

Targets

Details
1. Cytochrome P450 19A1
Kind
Protein
Organism
Humans
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]
  5. FDA Approved Drug Products: Femara Letrozole Oral Tablets [Link]
  6. FDA Approved Drug Products: Kisquali Femara Co-Pack Letrozole and Ribociclib Succinate Oral Tablets [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
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. Azria D, Larbouret C, Cunat S, Ozsahin M, Gourgou S, Martineau P, Evans DB, Romieu G, Pujol P, Pelegrin A: Letrozole sensitizes breast cancer cells to ionizing radiation. Breast Cancer Res. 2005;7(1):R156-63. doi: 10.1186/bcr969. Epub 2004 Dec 7. [PubMed:15642164]
  2. Trosken ER, Fischer K, Volkel W, Lutz WK: Inhibition of human CYP19 by azoles used as antifungal agents and aromatase inhibitors, using a new LC-MS/MS method for the analysis of estradiol product formation. Toxicology. 2006 Feb 15;219(1-3):33-40. doi: 10.1016/j.tox.2005.10.020. Epub 2005 Dec 5. [PubMed:16330141]
  3. Dowsett M, Jones A, Johnston SR, Jacobs S, Trunet P, Smith IE: In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clin Cancer Res. 1995 Dec;1(12):1511-5. [PubMed:9815951]
  4. FDA Approved Drug Products: Femara Letrozole Oral Tablets [Link]
  5. FDA Approved Drug Products: Kisquali Femara Co-Pack Letrozole and Ribociclib Succinate Oral Tablets [Link]
Kind
Protein
Organism
Humans
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. 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]
  2. Bhatnagar AS: The discovery and mechanism of action of letrozole. Breast Cancer Res Treat. 2007;105 Suppl 1:7-17. doi: 10.1007/s10549-007-9696-3. Epub 2007 Oct 3. [PubMed:17912633]
  3. FDA Approved Drug Products: Femara Letrozole Oral Tablets [Link]
  4. FDA Approved Drug Products: Kisquali Femara Co-Pack Letrozole and Ribociclib Succinate Oral Tablets [Link]
Kind
Protein
Organism
Humans
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. 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]
  2. 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]
  3. Borrie AE, Rose RV, Choi YH, Perera FE, Read N, Sexton T, Lock M, Vandenberg TA, Hahn K, Dinniwell R, Younus J, Logan D, Potvin K, Yaremko B, Yu E, Lenehan J, Welch S, Tyndale RF, Teft WA, Kim RB: Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer. Breast Cancer Res Treat. 2018 Nov;172(2):371-379. doi: 10.1007/s10549-018-4910-z. Epub 2018 Aug 9. [PubMed:30094551]
  4. Bhatnagar AS: The discovery and mechanism of action of letrozole. Breast Cancer Res Treat. 2007;105 Suppl 1:7-17. doi: 10.1007/s10549-007-9696-3. Epub 2007 Oct 3. [PubMed:17912633]
  5. FDA Approved Drug Products: Femara Letrozole Oral Tablets [Link]
  6. FDA Approved Drug Products: Kisquali Femara Co-Pack Letrozole and Ribociclib Succinate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: Femara Letrozole Oral Tablets [Link]
  2. FDA Approved Drug Products: Kisquali Femara Co-Pack Letrozole and Ribociclib Succinate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Precht JC, Schroth W, Klein K, Brauch H, Krynetskiy E, Schwab M, Murdter TE: The letrozole phase 1 metabolite carbinol as a novel probe drug for UGT2B7. Drug Metab Dispos. 2013 Nov;41(11):1906-13. doi: 10.1124/dmd.113.053405. Epub 2013 Aug 21. [PubMed:23965986]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Bhatnagar AS: The discovery and mechanism of action of letrozole. Breast Cancer Res Treat. 2007;105 Suppl 1:7-17. doi: 10.1007/s10549-007-9696-3. Epub 2007 Oct 3. [PubMed:17912633]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Miyajima M, Kusuhara H, Takahashi K, Takashima T, Hosoya T, Watanabe Y, Sugiyama Y: Investigation of the effect of active efflux at the blood-brain barrier on the distribution of nonsteroidal aromatase inhibitors in the central nervous system. J Pharm Sci. 2013 Sep;102(9):3309-19. doi: 10.1002/jps.23600. Epub 2013 May 27. [PubMed:23712697]

Drug created on June 13, 2005 07:24 / Updated on October 27, 2020 11:13

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates