Exemestane

Exemestane competitively inhibits and time-dependently inactivates of human placental aromatase with Ki of 4.3 nM. Exemestane displaces [³H]DHT from rat prostate androgen receptor with IC50 of 0.9 μM. ^[1] Exemestane (1 μM) increases alkaline phosphatase activity in hFOB and Saos-2 cells and induces the expression of MYBL2, OSTM1, HOXD11, ADCYAP1R1, and glypican 2 in hFOB cells. ^[2] Exemestane causes aromatase degradation in a dose-responsive manner in MCF-7aro cells. ^[3]

Exemestane increases lumbar spine BMD by 14.0% in OVX rats at dose of 100 mg/kg. Exemestane (100 mg/kg) and 17-hydroexemestane (20 mg/kg) significantly reduces an ovariectomy-induced increase in serum pyridinoline and serum osteocalcin in rats and causes significant reductions of serum cholesterol and low-density lipoprotein cholesterol inOVX rats. ^[4] Exemestane (20 mg/kg/day s.c.) induces 26% complete (CR) and 18% partial (PR) tumor regressions in rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors. ^[5]

• 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.

• Cell lines

  hFOB cells

• Concentrations

  1 μM

• Incubation Time

  24 hours

• Method

  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

• Animal Models

  estrogen-deficient ovariectomized (OVX) rats

• Dosages

  100 mg/kg

• Administration

  Intramuscular injection