WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100510
Description: Letrozole, also known as CGS-20267, is a nonsteroidal inhibitor of estrogen synthesis with antineoplastic activity. As a third-generation aromatase inhibitor, letrozole selectively and reversibly inhibits aromatase, which may result in growth inhibition of estrogen-dependent breast cancer cells. Aromatase, a cytochrome P-450 enzyme localized to the endoplasmic reticulum of the cell and found in many tissues including those of the premenopausal ovary, liver, and breast, catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis.
MedKoo Cat#: 100510
Chemical Formula: C17H11N5
Exact Mass: 285.10145
Molecular Weight: 285.3
Elemental Analysis: C, 71.57; H, 3.89; N, 24.55
Synonym: CGS20267; CGS-20267; CGS 20267; Abbreviation: LTZ. Brand name: Femara; Letoval.
IUPAC/Chemical Name: 4-[(4-cyanophenyl)-(1,2,4-triazol-1-yl)methyl]benzonitrile
InChi Key: HPJKCIUCZWXJDR-UHFFFAOYSA-N
InChi Code: 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
SMILES Code: N#CC1=CC=C(C(C2=CC=C(C#N)C=C2)N3N=CN=C3)C=C1
Appearance: White to light yellow crystalline powder.
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Letrozole (CGS 20267) is a potent, selective, reversible, and non-steroidal inhibitor of aromatase with an IC50 of 11.5 nM|
|In vitro activity:||This study investigated the effect of letrozole on bone metabolism, focusing on osteoclastogenesis. Letrozole did not affect the viability, proliferation, or migration of bone marrow-derived macrophages (BMMs); however, it reduced the multinucleation of immature osteoclasts and subsequent bone resorption in vitro. Overall, letrozole inhibited the expression of dendritic cell-specific transmembrane protein (DC-STAMP), tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K. Among them, the reduced expression of DC-STAMP was the most prominent. However, this downregulation of DC-STAMP expression following letrozole treatment was not related to the inhibition of major osteoclastogenesis pathways, such as the nuclear factor-κB (NF-κB), cFos, and nuclear factor of activated T cell c1 (NFATc1) pathways, but was attributed to the inhibition of p38, which is known to reside upstream of DC-STAMP expression. Notably, the anti-osteoclastogenic effect of letrozole was abolished following treatment with the p38 activator anisomycin. Contrary to expectations, these results strongly suggest a previously unknown anti-osteoclastogenic activity of letrozole, mediated by the downregulation of the p38/DC-STAMP pathway. Int J Mol Sci. 2020 Nov 9;21(21):8396. https://pubmed.ncbi.nlm.nih.gov/33182361/|
|In vivo activity:||In this study, it was investigated whether letrozole treatment of pubertal female mice exerts organizational or activational effects on host physiology and the gut microbiome. In previous findings, letrozole treatment of female mice resulted in weight gain and abdominal adiposity compared to placebo mice. In this cohort, 5 weeks of letrozole treatment also resulted in increased body weight (Fig 4A). When body weight and parametrial fat were measured at the end of the experiment, placebo and letrozole-treated mice had similar body weights and amounts of parametrial fat relative to body weight post-pellet removal (Fig 4A and 4B). Since changes in the gut microbiome were reported to correlate with PCOS in both women and in rodent models, it was investigated whether letrozole treatment resulted in organizational or activational effects on the composition of the gut microbiome. The species richness (alpha diversity) of the gut microbiome in placebo and letrozole-treated female mice was analyzed using Faith’s PD estimate before (weeks 1–5) and after (weeks 9–13) pellet removal (Fig 6A). Similar to a previous report, placebo mice showed a significant positive correlation with alpha diversity during the first 5 weeks of the study that corresponded with puberty. In contrast, letrozole treatment of pubertal female mice did not result in a significant change in alpha diversity over time (RM-ANOVA: p = 0.059) (Fig 6A). After pellet removal, placebo mice did not demonstrate a positive correlation with alpha diversity over time and letrozole mice demonstrated similar alpha diversity to placebo-treated mice (Fig 6A). This study clearly showed that letrozole treatment of pubertal female mice resulted in activational effects on the reproductive axis. PLoS One. 2019; 14(9): e0223274. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768472/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 285.3 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Kim HJ, Seong HS, Choi Y, Heo SC, Kim YD. Letrozole Suppresses the Fusion of Osteoclast Precursors through Inhibition of p38Mediated DC-STAMP Pathway. Int J Mol Sci. 2020 Nov 9;21(21):8396. doi: 10.3390/ijms21218396. PMID: 33182361; PMCID: PMC7664929. 2. 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. PMID: 25695958; PMCID: PMC4631403. 3. Arroyo P, Ho BS, Sau L, Kelley ST, Thackray VG. Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome. PLoS One. 2019 Sep 30;14(9):e0223274. doi: 10.1371/journal.pone.0223274. PMID: 31568518; PMCID: PMC6768472. 4. Torres PJ, Ho BS, Arroyo P, Sau L, Chen A, Kelley ST, Thackray VG. Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model. Endocrinology. 2019 May 1;160(5):1193-1204. doi: 10.1210/en.2019-00050. PMID: 30924862; PMCID: PMC6482036.|
|In vitro protocol:||1. Kim HJ, Seong HS, Choi Y, Heo SC, Kim YD. Letrozole Suppresses the Fusion of Osteoclast Precursors through Inhibition of p38Mediated DC-STAMP Pathway. Int J Mol Sci. 2020 Nov 9;21(21):8396. doi: 10.3390/ijms21218396. PMID: 33182361; PMCID: PMC7664929. 2. 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. PMID: 25695958; PMCID: PMC4631403.|
|In vivo protocol:||1. Arroyo P, Ho BS, Sau L, Kelley ST, Thackray VG. Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome. PLoS One. 2019 Sep 30;14(9):e0223274. doi: 10.1371/journal.pone.0223274. PMID: 31568518; PMCID: PMC6768472. 2. Torres PJ, Ho BS, Arroyo P, Sau L, Chen A, Kelley ST, Thackray VG. Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model. Endocrinology. 2019 May 1;160(5):1193-1204. doi: 10.1210/en.2019-00050. PMID: 30924862; PMCID: PMC6482036.|
1: Keskin U, Ercan CM, Yilmaz A, Babacan A, Korkmaz C, Duru NK, Ergun A. Random-start controlled ovarian hyperstimulation with letrozole for fertility preservation in cancer patients: case series and review of literature. J Pak Med Assoc. 2014 Jul;64(7):830-2. Review. PubMed PMID: 25255597.
2: Liu A, Zheng C, Lang J, Chen W. Letrozole versus clomiphene citrate for unexplained infertility: a systematic review and meta-analysis. J Obstet Gynaecol Res. 2014 May;40(5):1205-16. doi: 10.1111/jog.12393. Review. PubMed PMID: 24754848.
3: Song Y, Li Z, Wu X, Wang X, Xiao J, Wang B. Effectiveness of the antagonist/letrozole protocol for treating poor responders undergoing in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Gynecol Endocrinol. 2014 May;30(5):330-4. doi: 10.3109/09513590.2013.875997. Epub 2014 Jan 24. Review. PubMed PMID: 24456013.
4: Fan L, Liedke PE, Isakoff SJ, St Louis J, Ryan PD, Goss PE. Intermittent letrozole therapy for metastatic breast cancer: case reports and literature review. Clin Breast Cancer. 2014 Apr;14(2):e41-5. doi: 10.1016/j.clbc.2013.10.009. Epub 2013 Oct 25. Review. PubMed PMID: 24342729.
5: Dahhan T, Balkenende E, van Wely M, Linn S, Goddijn M. Tamoxifen or letrozole versus standard methods for women with estrogen-receptor positive breast cancer undergoing oocyte or embryo cryopreservation in assisted reproduction. Cochrane Database Syst Rev. 2013 Nov 8;11:CD010240. doi: 10.1002/14651858.CD010240.pub2. Review. PubMed PMID: 24213953.
6: Kar S. Current evidence supporting "letrozole" for ovulation induction. J Hum Reprod Sci. 2013 Apr;6(2):93-8. doi: 10.4103/0974-1208.117166. Review. PubMed PMID: 24082649; PubMed Central PMCID: PMC3778612.
7: Riemsma R, Forbes CA, Amonkar MM, Lykopoulos K, Diaz JR, Kleijnen J, Rea DW. Systematic review of lapatinib in combination with letrozole compared with other first-line treatments for hormone receptor positive(HR+) and HER2+ advanced or metastatic breast cancer(MBC). Curr Med Res Opin. 2012 Aug;28(8):1263-79. doi: 10.1185/03007995.2012.707643. Epub 2012 Jul 16. Review. PubMed PMID: 22738819.
8: Cohen MH, Johnson JR, Justice R, Pazdur R. Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. Oncologist. 2011;16(12):1762-70. doi: 10.1634/theoncologist.2011-0287. Epub 2011 Nov 16. Review. PubMed PMID: 22089970; PubMed Central PMCID: PMC3248775.
9: Barnadas A, Estévez LG, Lluch-Hernández A, Rodriguez-Lescure A, Rodriguez-Sanchez C, Sanchez-Rovira P. An overview of letrozole in postmenopausal women with hormone-responsive breast cancer. Adv Ther. 2011 Dec;28(12):1045-58. doi: 10.1007/s12325-011-0075-4. Epub 2011 Nov 7. Review. PubMed PMID: 22068628.
10: Regan MM, Price KN, Giobbie-Hurder A, Thürlimann B, Gelber RD; International Breast Cancer Study Group and BIG 1-98 Collaborative Group. Interpreting Breast International Group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer. Breast Cancer Res. 2011 May 26;13(3):209. doi: 10.1186/bcr2837. Review. PubMed PMID: 21635709; PubMed Central PMCID: PMC3218925.
11: He D, Jiang F. Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome. Reprod Biomed Online. 2011 Jul;23(1):91-6. doi: 10.1016/j.rbmo.2011.03.024. Epub 2011 Apr 3. Review. PubMed PMID: 21550852.
12: Steed HL, Chu QS. Aromatase inhibition: a potential target for the management of recurrent or metastatic endometrial cancer by letrozole: more questions than answers? Expert Opin Investig Drugs. 2011 May;20(5):681-90. doi: 10.1517/13543784.2011.566862. Epub 2011 Mar 18. Review. PubMed PMID: 21413907.
13: Geisler J. Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole--of clinical importance? Br J Cancer. 2011 Mar 29;104(7):1059-66. doi: 10.1038/bjc.2011.58. Epub 2011 Mar 1. Review. PubMed PMID: 21364577; PubMed Central PMCID: PMC3068499.
14: Merriam P, Sikov WM. Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer. Breast Cancer (Dove Med Press). 2011 Oct 26;3:139-50. doi: 10.2147/BCTT.S12150. Review. PubMed PMID: 24367183; PubMed Central PMCID: PMC3846896.
15: Pritts EA. Letrozole for ovulation induction and controlled ovarian hyperstimulation. Curr Opin Obstet Gynecol. 2010 Aug;22(4):289-94. doi: 10.1097/GCO.0b013e32833beebf. Review. PubMed PMID: 20592587.
16: Sylvestre VT, Dunton CJ. Treatment of recurrent endometrial stromal sarcoma with letrozole: a case report and literature review. Horm Cancer. 2010 Apr;1(2):112-5. doi: 10.1007/s12672-010-0007-9. Epub 2010 Jan 29. Review. PubMed PMID: 21761354.
17: Dellapasqua S, Colleoni M. Letrozole. Expert Opin Drug Metab Toxicol. 2010 Feb;6(2):251-9. doi: 10.1517/17425250903540246. Review. PubMed PMID: 20095792.
18: Guarneri V. Lapatinib plus letrozole for postmenopausal patients with advanced HER2(+)/HR(+) breast cancer. Expert Rev Anticancer Ther. 2009 Nov;9(11):1549-57. doi: 10.1586/era.09.124. Review. PubMed PMID: 19895239.
19: Keating GM. Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. Drugs. 2009 Aug 20;69(12):1681-705. doi: 10.2165/10482340-000000000-00000. Review. PubMed PMID: 19678717.
20: Nabholtz JM, Mouret-Reynier MA, Durando X, Van Praagh I, Al-Sukhun S, Ferriere JP, Chollet P. Comparative review of anastrozole, letrozole and exemestane in the management of early breast cancer. Expert Opin Pharmacother. 2009 Jun;10(9):1435-47. doi: 10.1517/14656560902953738. Review. PubMed PMID: 19445563.
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 medications such as bisphosphonates.
Femara tablets for oral administration contains 2.5 mg of letrozole, a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis). Letrozole is a white to yellowish crystalline powder, practically odorless, freely soluble in dichloromethane, slightly soluble in ethanol, and practically insoluble in water. It has a molecular weight of 285.31, empirical formula C17H11N5, and a melting range of 184Â°C-185Â°C. Femara is available as 2.5 mg tablets for oral administration. Inactive Ingredients: Colloidal silicon dioxide, ferric oxide, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, talc, and titanium dioxide.
According to http://en.wikipedia.org/wiki/Letrozole, Letrozole has been used for ovarian stimulation by fertility doctors since 2001Â—having less side-effects than Clomiphene Citrate (Clomid) and less chance of multiple gestation. A Canadian study presented at the American Society of Reproductive Medicine 2005 Conference suggests that Letrozole may increase the risk of birth defects . A more detailed ovulation induction follow-up study found that Letrozole, compared with a control group of Clomiphene Citrate, had significantly lower congenital malformations and chromosomal abnormalities at an overall rate of 2.4% (1.2% major malformations) compared with Clomiphene Citrates 4.8% (3.0% major malformations). However, the use of Letrozole is not intended for ovulation induction, and the manufacturer, Novartis, has issued letters to doctors in Canada and the United States reiterating that it is not approved for such a use and is not safe to use with pregnant women or women who may become pregnant. 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. Some studies have shown that Letrozole can be used to promote spermatogenesis in male patients suffering from nonobstructive azoospermia. Letrozole has also been shown to delay the fusing of the growth plates in mice. When used with growth hormone, Letrozole has been shown thereputic for adolescents and children with short stature. Letrozole has also been used to treat endometriosis.
Mechanism of Action
The growth of some cancers of the breast is stimulated or maintained by estrogens. 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 is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens. In adult nontumor- and tumor-bearing female animals, letrozole is as effective as ovariectomy in reducing uterine weight, elevating serum LH, and causing the regression of estrogen-dependent tumors. In contrast to ovariectomy, treatment with letrozole does not lead to an increase in serum FSH. 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.