Letrozole (Synonyms: CGS 20267)

Letrozole is a novel and potent type (II) aromatase inhibitor with IC50 of 11.5 nM. It belongs to the reversible non-steroidal compound family which can inhibit Arom. However, there is no evidence that it can affect the adrenal steroidogenesis.[1]

Normally, Type II inhibitors have a common feature of heterocyclic azole moiety, which can be binded to the heme–iron in aromatase. It contains a structure of 1,2,4-triazole moieties which can coordinate the heme–iron of cytochrome P450. Meanwhile, benzonitrile substituted letrozole can mimic a unique enzyme structure of the substrate androstenedione.[2]

Letrozole administration can reduce spine synapse and axon outgrowth and it also will decrease the expression of estrogen receptor  (ER). While, the synaptic proteins including GAP-43 can impaire the long-termpotentiation.[1] Letrozole is proved to promote FSH release from the hypothalamic pituitary axis by responding to decreased estrogen (E) feedback.[3]

References:
[1] Chen Bian, Yangang Zhao, Qiang Guo, Ying Xiong, Wenqin Cai, Jiqiang Zhang. Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocrine and integration. The Journal of Steroid Biochemistry and Molecular Biology. May 2014. 141: 37-43.
[2] Hakki Türker Akçay, Riza Bayrak. Computational studies on the anastrozole and letrozole, effective chemotherapy drugs against breast cancer. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 25 March 2014. 122: 142-152.
[3] Lindsay Malloch, Alice Rhoton-Vlasak. An assessment of current clinical attitudes toward letrozole use in reproductive endocrinology practices. Fertility and Sterility. December 2013. 100(6): 1740-1744.