Exemestane (EXE) is an Aromatase Inhibitor. The mechanism of action of exemestane is as an Aromatase Inhibitor.

Aromatase (human):30 nM, Aromatase (rat):40 nM

在7,12-二甲基苯并蒽（DMBA）诱导的乳房肿瘤大鼠中,每天皮下注射20 mg/kg Exemestane诱导26％完全（CR）和18％部分（PR）肿瘤消退.Exemestane在OVX大鼠中以100 mg/kg的剂量使腰椎BMD增加14.0％.Exemestane（100 mg/kg）和17-hydroexemestane（20 mg/kg）显著降低卵巢切除诱导的大鼠血清吡啶啉和血清骨钙素的增加,并导致OVX大鼠血清胆固醇和低密度脂蛋白胆固醇显著降低.

Exemestane（1 μM）增加hFOB和Saos-2细胞中的碱性磷酸酶活性,并诱导hFOB细胞中MYBL2,OSTM1,HOXD11,ADCYAP1R1和磷脂酰肌醇蛋白聚糖2的表达。Exemestane以4.3 nM的Ki竞争性抑制和时间依赖性地灭活人胎盘芳香酶。Exemestane替代大鼠前列腺雄激素受体的[3 H] DHT,IC50为0.9 μM。Exemestane在MCF-7aro细胞中以剂量响应方式引起芳香酶降解。

Assays with human placental aromatase: Microsomes are prepared from human placenta and stored at -80℃. The rate of aromatization is determined by measuring the tritiated water released from [1β-3H]A. The assay is carried out in a final volume of 1 mL, in 10 mM phosphate buffer, pH 7.5, containing 100 mM KCl, 1 mM EDTA, 1 mM dithiothreitol, 100 μM NADPH, the enzyme preparation and the appropriate concentrations of Exemestane (in duplicate) and the substrate. After a 10 min incubation at 37 ℃, the assay is terminated by the addition of 4 mL cold chloroform. The acqueous phase is treated with a charcoal suspension, the supernatant is removed and counted for radioactivity by liquid scintillation in Rialuma. For the determination of the IC50 values, various concentrations of Exemestane are incubated with 20 μg of microsomal protein, in the presence of a fixed amount (50 nM) of [3H]A.

hFOB is treated with steroids and Exemestane for 24 hours, when specimens are harvested and evaluated for cell proliferation using the WST-8 method. Optical densities (OD, 450 nm) are evaluated using a SpectraMax 190 microplate reader and Softmax Pro 4.3 microplate analysis software. The status of proliferation (%) is calculated according to the following equation: (cell OD value after test materials treated /vehicle control cell OD value)× 10(Only for Reference)