Letrozole-d4 is intended for use as an internal standard for the quantification of letrozole by GC- or LC-MS. Letrozole is a potent, cell-permeable inhibitor of aromatase (IC50 = 2 nM).1 It inhibits proliferation of estrogen receptor-positive (ER+) MCF-7 cells when used alone at concentrations ranging from 0.1 to 100 nM and when used at a concentration of 10 nM in combination with testosterone or 4-androstene-3,17-dione.2 It also reduces matrix metalloproteinase-2 (MMP-2) and MMP-9 levels in MCF-7 cells when used at a concentration of 10 nM. Letrozole (10 µg per day) reduces tumor growth in an MCF-7Ca ovariectomized-mouse xenograft model.3 Formulations containing letrozole have been used in the treatment of postmenopausal breast cancer.4
1.Mayhoub, A.S., Marler, L., Kondratyuk, T.P., et al.Optimization of the aromatase inhibitory activities of pyridylthiazole analogues of resveratrolBioorg. Med. Chem.20(7)2427-2434(2012) 2.Mitropoulou, T.N., Tzanakakis, G.N., Kletsas, D., et al.Letrozole as a potent inhibitor of cell proliferation and expression of metalloproteinases (MMP-2 and MMP-9) by human epithelial breast cancer cellsInt. J. Cancer104(2)155-160(2003) 3.Long, B.J., Jelovac, D., Handratta, V., et al.Therapeutic strategies using the aromatase inhibitor letrozole and tamoxifen in a breast cancer modelJ. Natl. Cancer Inst.96(6)456-465(2004) 4.Cohen, M.H., Johnson, J.R., Li, N., et al.Approval summary: Letrozole in the treatment of postmenopausal women with advanced breast cancerClin Cancer Res.8(3)665-669(2002)