Letrozole
LETROZOL · FEMARA · LETRAZOLE · LetrozoleUsp28 · Letrozole(FeMara) · Letroz · etrozoL · Lelrozol
Identifiers & Physical Properties
| CAS No. | 112809-51-5 |
|---|---|
| Molecular formula | C17H11N5 |
| Average molar mass | 285.3 g/mol |
| Monoisotopic mass | 285.10144535 g/mol |
| SMILES | N#Cc1ccc(C(c2ccc(C#N)cc2)n2cncn2)cc1 |
| InChIKey | HPJKCIUCZWXJDR-UHFFFAOYSA-N |
| PubChem CID | 3902 |
| ChEMBL | CHEMBL1444 |
| ChEBI | CHEBI:6413 |
| EC No. | 675-034-8 |
| DTXSID | DTXSID4023202 |
Chemical & Physical Properties
| XLogP | 2.7 |
|---|---|
| Topological polar surface area | 78.3 |
| Hydrogen bond donors | 0 |
| Hydrogen bond acceptors | 4 |
| Rotatable bonds | 3 |
| Heavy atoms | 22 |
| Formal charge | 0 |
| Complexity | 420 |
| Drugs | PharmaceuticalsPharmaceuticals -> Listed in ZINC15 |
| LogP (partition coefficient) | 2.51.84 |
| Odor | Practically odorless |
| Color/Form | White to yellowish crystalline powder |
| Solubility | Freely soluble in dichloromethaneslightly soluble in ethanolpractically insoluble in water7.99e-02 g/LDMSO: >50mg/mL |
| Human Drugs | Breast FeedingLactationMilk, HumanAntineoplastic AgentsAromatase InhibitorsFDA approved drugs -> Active ingredientPharmaceuticalsOvulation inducers |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| Melting point | 184-185 °C181-183 °C184 - 185 °C181-183°C |
| Physical Description | Solid |
| Collision Cross Section | 166.5 Ų [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: TOXCASTSource Identifier: DTXSID4023202] |
| Boiling point | 563.5±60.0 °C(Predicted) |
| Density | 1.21±0.1 g/cm3(Predicted) |
| Storage conditions | 2-8°C |
| Physical state | White powder |
| pKa (acidity coefficient) | 1.52±0.11(Predicted) |
| Color | white to off-white |
| Merck | 14,5450 |
| 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 |
| InChIKey | HPJKCIUCZWXJDR-UHFFFAOYSA-N |
| SMILES | C(C1=CC=C(C=C1)C#N)(C1=CC=C(C=C1)C#N)N1C=NC=N1 |
| CAS DataBase Reference | 112809-51-5(CAS DataBase Reference) |
| NCI Dictionary of Cancer Terms | Femaraletrozole |
| FDA UNII | 7LKK855W8I |
| NCI Drug Dictionary | Femara |
| ATC code | L02BG04 |
| UNSPSC Code | 51111800 |
| NACRES | NA.77 |
| Protein binding | 60% |
| Excreted unchanged in urine | 6% |
| Volume of distribution | 1.87(L/kg) |
| Biological half-life | 48 / Unchanged |
| GHS pictogram | GHS08 |
| Signal word | Warning |
| GHS hazard statements | H361fd-H373 |
| GHS precautionary statements | P202-P260-P280-P308+P313-P405-P501 |
| Hazard symbols | Xi |
| Risk statements (R) | 36/37/38 |
| Safety statements (S) | 26-36 |
| Water hazard class (WGK) | 3 |
| RTECS number | DI4957000 |
| Customs code | 2933997500 |
| Storage class | 11 - Combustible Solids |
| Hazard class | Repr. 2STOT RE 2 |
| Hazardous substances data | 112809-51-5(Hazardous Substances Data) |
Safety & Regulations
| GHS classification | DangerH315 (29.5%): Causes skin irritation [Warning Skin corrosion/irritation]P203, P260, P264, P264+P265, P280, P302+P352, P305+P351+P338, P318, P319, P321, P332+P317, P337+P317, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 44 reports by companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatory information | Letrozole: Does not have an individual approval but may be used under an appropriate group standard |
| FDA requirements | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl letrozole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Hazard Classes and Categories | Skin Irrit. 2 (29.5%) |
| Shipment Methods and Regulations | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/ |
| Cleanup methods | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair)low-permeability, disposable protective garments (coveralls or gown and shoe covers)safety glasses or splash gogglesrespiratorabsorbent, plastic-backed sheets or spill pads |
Applications & Uses
Description
Letrozole, also known as Femara, is an orally active aromatase inhibitor that works by competitively inhibiting aromatase. This inhibition prevents the conversion of androgens to estrogen (estrogen stimulates breast tissues and breast cancer reoccurrence) and gonadal steroidogenesis. It can be used for the treatment of breast cancer that is hormonally-responsive or has an unknown receptor status in postmenopausal women. Besides this, Letrozole also has some off-label use such as ovarian stimulation, pretreatment of termination of pregnancy, treatment of gynecomastia, treatment of endometriosis, and promoting spermatogenesis for male patients of nonobstructive azoospermia.
History
Letrozole was discovered by scientists at the Swiss company Ciba-Geigy AG (now Novartis AG) In the 1980s while screening compounds for their ability to inhibit aromatase. Letrozole was far more potent than any other aromatase inhibitor discovered. As a result, its development was accelerated, leading to its approval in 1996 for the treatment of advanced breast cancer in France and other European countries. The following year letrozole was approved by the U.S. Food and Drug Administration. In addition to the drug’s general approval for the treatment of advanced breast cancer, in later years it was approved for multiple and specific applications. For example, in 2001 letrozole was approved in the United Kingdom specifically for the first-line treatment of advanced breast cancer, and in 2004 it was approved in the United States for what is known as extended adjuvant therapy.
Uses
A nonsteroidal aromatase inhibitor structurally related to Fadrozole. Antineoplastic
Uses
Letrozole has been used:in organoid growth assay to determine its inhibitory capacity(48) to investigate steroid receptor coactivator-1 (SRC-1) mediated endogenous estrogen regulation of hippocampal PSD-95(49) to determine its effects on tumor-induced hyperalgesia(50) for hormonal manipulation in rats(51) to study its effects on lipocalin-2 (Lcn2)(52) to determine its effects on mechanical hyperalgesia and aromatase expression(53)
General Description
Letrozole, 4,4'-(1H-1,2,4-triazol-1-ylmethylene)dibenzonitrile (Femara), is used for most of thesame indications as anastrozole. It reduces concentrations ofestrogens by 75% to 95%, with maximal suppressionachieved within 2 to 3 days. Letrozole is specific for aromataseinhibition, with no additional effects on adrenal corticoidbiosynthesis. CYPs 3A4 and 2A6 are involved in themetabolism of letrozole to the major carbinol metabolite,which is inactive. The loss of the triazole ring, which is involvedin coordination of the heme iron, would explain theloss of activity. Letrozole strongly inhibits CYP2A6 invitro, with moderate inhibition of CYP2C19. The effect ofthis in vitro inhibition on the pharmacokinetics of coadministereddrugs is unknown. Tamoxifen reduces the levels ofletrozole significantly if they are used together, so combinationtreatment with these agents is not recommended.