Atrasentan CAS# 173937-91-2 (2R,3R,4S)-4-(1,3-苯并二氧戊环-5-基)-1-[2-(二丁基氨基)-2-氧代乙基]-2-(4-甲氧基苯基)吡咯烷-3-羧酸

Atrasentan is a selective endothelin-A (ET_A) receptor antagonist developed primarily for cardiovascular and renal indications, particularly diabetic nephropathy and prostate cancer. In preclinical studies, Atrasentan demonstrated potent inhibition of ET-1–induced vasoconstriction and smooth muscle cell proliferation with high selectivity for the ET_A receptor (Ki ≈ 0.034 nM for ET_A vs 45 nM for ET_B; >1000-fold selectivity). In rodent and canine models of hypertension and renal injury, oral administration of Atrasentan (0.1–10 mg/kg) significantly reduced mean arterial pressure, proteinuria, and glomerulosclerosis without markedly affecting heart rate. In models of diabetic nephropathy, Atrasentan attenuated mesangial expansion, reduced urinary albumin excretion by up to 60%, and decreased renal transforming growth factor-β (TGF-β) expression, consistent with anti-fibrotic and anti-inflammatory effects. Additionally, in tumor xenograft models (e.g., prostate carcinoma), Atrasentan inhibited tumor growth and angiogenesis, likely via blockade of ET-1–mediated autocrine signaling.