| 生化机理 |
Description:
IC50 Value: 0.0551 nM (for ET A receptor) [1]
Atrasentan (A-147627) is an endothelin antagonist receptor being developed at Abbott Laboratories for the treatment of prostate cancer.
in vitro: The combination of Atrasentan with Taxotere was more effective in the inhibition of cell viability and induction of apoptosis in LNCaP and C4-2b cells (androgen receptor positive) but not in PC-3 cells[2]. Atrasentan profoundly induced several CYPs and drug transporters (e.g. 12-fold induction of CYP3A4 at 50 μM). It was a moderate P-gp inhibitor (IC(50) in P388/dx cells = 15.1 ± 1.6 μM) and a weak BCRP inhibitor (IC(50) in MDCKII-BCRP cells = 59.8 ± 11 μM). BCRP or P-gp overexpressing cells were slightly more resistant towards antiproliferative effects of atrasentan [5].
in vivo: ABT-627 did reduce the accumulation of macrophages in both stains (36 to 53%) whereas it blocked by 76% the influx of eosinophils in Balb/c but not in C57Bl/6 mice [3]. Atrasentan was administered orally via drinking water at 3 mg kg-1 per day over 28 days. All diabetic mice developed similar hyperglycaemia (27-30 mmol l-1). Atrasentan treatment significantly improved left ventricular systolic and diastolic function in response to exogenous norepinephrine, but there were no differences between genotypes [4].
Clinical trial: Atrasentan and Zometa for Men With Prostate Cancer Metastatic to Bone . Phase2
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