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Product Details:

  • CAS No: 112809-51-5
  • AHFC code: 10:00.0
  • Synonyms: Letrozol
  • ATC Code: L02BG04
  • Chemical Formula: C21H31N3O5
  • Molecular Weight: 285.3027
  • Assay/Purity: Typically NLT 98%
  • DrugBank: DB01006 (APRD01066)
  • SMILES: N#CC1=CC=C(C=C1)C(N1C=NC=N1)C1=CC=C(C=C1)C#N
  • InChl: HPJKCIUCZWXJDR-UHFFFAOYSA-N
  • PubChem: 3902
  • IUPAC: 4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]benzonitrile

Additional Details

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.
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.
Mode 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.
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.
Toxicity:
General Reference:
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
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