Letrozole related compound B | CAS#112809-52-6 | aromatase inhibitor impurity

MedKoo Cat#: 598624 | Name: Letrozole related compound B

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Letrozole related compound B is an aromatase inhibitor impurity.

Chemical Structure

Letrozole related compound B

CAS#112809-52-6

Theoretical Analysis

MedKoo Cat#: 598624

Name: Letrozole related compound B

CAS#: 112809-52-6

Chemical Formula: C17H11N5

Exact Mass: 285.1014

Molecular Weight: 285.31

Elemental Analysis: C, 71.57; H, 3.89; N, 24.55

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Synonym

Letrozole related compound B; Letrozole specified impurity A;

IUPAC/Chemical Name

4,4'-((4H-1,2,4-triazol-4-yl)methylene)dibenzonitrile

InChi Key

BCTXUGAAOFIJGX-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H11N5/c18-9-13-1-5-15(6-2-13)17(22-11-20-21-12-22)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=C2)C#N)N3C=NN=C3)C=C1

Appearance

Solid 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

Shelf Life

>3 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

2934.99.03.00

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Letrozole related compound B is an aromatase inhibitor impurity.

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), c-Fos, 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/

Preparing Stock Solutions

The following data is based on the product molecular weight 285.31 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 p38-Mediated 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:

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: Roque M, Tostes AC, Valle M, Sampaio M, Geber S. Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis. Gynecol Endocrinol. 2015;31(12):917-21. doi: 10.3109/09513590.2015.1096337. Epub 2015 Oct 19. Review. PubMed PMID: 26479460. 2: Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16. PubMed PMID: 25524798. 3: 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. 4: Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. PubMed PMID: 27959613. 5: Xi W, Liu S, Mao H, Yang Y, Xue X, Lu X. Use of letrozole and clomiphene citrate combined with gonadotropins in clomiphene-resistant infertile women with polycystic ovary syndrome: a prospective study. Drug Des Devel Ther. 2015 Nov 11;9:6001-8. doi: 10.2147/DDDT.S83259. eCollection 2015. PubMed PMID: 26648691; PubMed Central PMCID: PMC4651359. 6: Li SJ, Zhang YJ, Chai XS, Nie MF, Zhou YY, Chen JL, Tao GS. Letrozole ovulation induction: an effective option in endometrial preparation for frozen-thawed embryo transfer. Arch Gynecol Obstet. 2014 Mar;289(3):687-93. Epub 2013 Oct 10. PubMed PMID: 24121690. 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 PMID: 25695958; PubMed Central PMCID: PMC4631403. 8: Ketkaew C, Kiatying-Angsulee N. Drug Use Evaluation of Letrozole in Breast Cancer Patients at Regional Cancer Hospitals in Thailand. Asian Pac J Cancer Prev. 2015;16(14):6055-9. PubMed PMID: 26320495. 9: Curley MD, Sabnis GJ, Wille L, Adiwijaya BS, Garcia G, Moyo V, Kazi AA, Brodie A, MacBeath G. Seribantumab, an Anti-ERBB3 Antibody, Delays the Onset of Resistance and Restores Sensitivity to Letrozole in an Estrogen Receptor-Positive Breast Cancer Model. Mol Cancer Ther. 2015 Nov;14(11):2642-52. doi: 10.1158/1535-7163.MCT-15-0169. Epub 2015 Aug 26. PubMed PMID: 26310543. 10: Wang HY, Zheng PS. A comparison of the efficacy of two doses of letrozole alone or with continuous recombinant follicle-stimulating hormone for ovulation induction in anovulatory women. Gynecol Obstet Invest. 2015;79(4):250-5. doi: 10.1159/000367847. Epub 2014 Nov 22. PubMed PMID: 25428607. 11: Rashid D, Panda BP, Vohora D. Reduced estradiol synthesis by letrozole, an aromatase inhibitor, is protective against development of pentylenetetrazole-induced kindling in mice. Neurochem Int. 2015 Nov;90:271-4. doi: 10.1016/j.neuint.2015.10.001. Epub 2015 Oct 9. PubMed PMID: 26449311. 12: Sharma S, Ghosh S, Singh S, Chakravarty A, Ganesh A, Rajani S, Chakravarty BN. Congenital malformations among babies born following letrozole or clomiphene for infertility treatment. PLoS One. 2014 Oct 1;9(10):e108219. doi: 10.1371/journal.pone.0108219. eCollection 2014. PubMed PMID: 25272289; PubMed Central PMCID: PMC4182712. 13: Singh AK, Srivastava PP, Verma R, Srivastava SC, Kumar D, Ansari A. Effect of dietary administration of letrozole and tamoxifen on gonadal development, sex differentiation and biochemical changes in common carp (Cyprinus carpio L.). Reprod Fertil Dev. 2015 Mar;27(3):449-57. doi: 10.1071/RD13234. PubMed PMID: 24411670. 14: Goldrat O, Gervy C, Englert Y, Delbaere A, Demeestere I. Progesterone levels in letrozole associated controlled ovarian stimulation for fertility preservation in breast cancer patients. Hum Reprod. 2015 Sep;30(9):2184-9. doi: 10.1093/humrep/dev155. Epub 2015 Jun 24. PubMed PMID: 26109617. 15: Zhao X, Zhang Q. [Clinical efficacy of letrozole in boys with idiopathic central precocious puberty]. Zhongguo Dang Dai Er Ke Za Zhi. 2014 Apr;16(4):397-400. Chinese. PubMed PMID: 24750838. 16: Yamaguchi M, Erdenebaatar C, Saito F, Motohara T, Miyahara Y, Tashiro H, Katabuchi H. Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma. Int J Gynecol Cancer. 2015 Nov;25(9):1645-51. doi: 10.1097/IGC.0000000000000557. PubMed PMID: 26495759. 17: Ecemis T, Tasci Y, Caglar GS. Controlled ovarian hyperstimulation with sequential letrozole co-treatment in normo/high responders. Gynecol Endocrinol. 2016;32(3):206-9. doi: 10.3109/09513590.2015.1110133. Epub 2015 Nov 20. PubMed PMID: 26487376. 18: Ganesh A, Chauhan N, Das S, Chakravarty B, Chaudhury K. Endometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles. Syst Biol Reprod Med. 2014 Apr;60(2):105-11. doi: 10.3109/19396368.2013.862316. Epub 2013 Dec 5. PubMed PMID: 24304327. 19: Bian C, Zhao Y, Guo Q, Xiong Y, Cai W, Zhang J. Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocrine and integration. J Steroid Biochem Mol Biol. 2014 May;141:37-43. doi: 10.1016/j.jsbmb.2013.12.020. Epub 2014 Jan 13. PubMed PMID: 24434281. 20: Li Z, Liu H, He Z, Zhang G, Lang J. Effects of cisplatin and letrozole on surgically induced endometriosis and comparison of the two medications in a rat model. Eur J Pharm Sci. 2016 Oct 10;93:132-40. doi: 10.1016/j.ejps.2016.07.018. Epub 2016 Jul 29. PubMed PMID: 27481456.