生物活性

• 靶点	HIF1α IC50:0.71±0.11μM

• 描述The response of mammalian cells to hypoxia is mediated by a family of transcription factors known as HIF (hypoxia-inducible factors). The subunits of HIF, HIF-1α and HIF-2α are structurally similar and can be degraded rapidly under normoxia. 2-Methoxyestradiol can inhibit HIF-1α and HIF-2α expression, as well as depolymerize microtubules. Treatment with 2-Methoxyestradiol (5 - 100 μM) for 16h can reduce expression of HIF-1α dose-dependently in PC-3 and MDA-MB-231 cells, accompanied with the reduced activity of HIF-1 and the expression of its target protein, VEGF, and without effect on HIF-1α mRNA levels or rate of protein degradation. Treatment with 2-Methoxyestradiol (10 - 100 μM) overnight can depolymerize microtubules and impair nuclear accumulation of HIF-1α in PC-3 cells under hypoxia. Daily oral administration of 2-Methoxyestradiol, 150 mg/kg, for 33 days suppressed tumor growth and angiogenesis, as well as depolymerized microtubules in breast cancer orthotopic models. The inhibition of HIF-2α expression and microtubule-depolymerization by 2-Methoxyestradiol can also be observed in endothelial cells^[1].
• 作用机制2-Methoxyestradiol inhibits the expression, nuclear accumulation and transcriptional activity of HIF-1α^[1]. However, the accurate mechanism of action is unknown now.

• 动物研究
  剂量	Rat: min = 0.1 mg/kg, max = 75 mg/kg[2] (p.o.); min = 60 mg/kg, max = 600 mg/kg[3] (i.p.)
  给药途径	p.o., i.p.
  动物药代数据	Animal Mice[4] Dose 100 mg/kg Administration p.o. Cmax 190 ng/ml (male) 35 ng/ml (female) Tmax 12 h (male) 30 h (female) F 90% (male) 190% (female) AUC 35.9 µM·min (male) 53.8 µM·min (female)