Atrasentan

Atrasentan (ABT-627) is an endothelin receptor antagonist with IC₅₀ of 0.0551 nM for ET_A^[1]. IC50 & Target:IC50: 0.055 nM (ET_A) In Vitro: Atrasentan (ABT-627, 0-50 μM) significantly inhibits LNCaP and C4-2b prostate cancer cell growth. ABT-627 in conbination with Taxotere elicits a significantly greater loss of viable prostate cancer cells relative to either agent alone and shows greater degree of down-regulation of the NF-κB DNA binding activity^[2]. Atrasentan profoundly induces several CYPs and drug transporters (e.g. 12-fold induction of CYP3A4 at 50 μM). It is a moderate P-gp inhibitor (IC₅₀ in P388/dx cells=15.1±1.6 μM) and a weak BCRP inhibitor (IC₅₀ in MDCKII-BCRP cells=59.8±11 μM)^[3]. In Vivo: Atrasentan (3 mg/kg, p.o.) inhibits the pressor response induced by big endothelin-1 (1 nmol/kg) in pithed rats^[1]. Aatrasentan (ABT-627, 10 mg/kg, i.p.) as well as Taxotere alone inhibited the C4-2b tumor growth within the bone environment to some extent in the SCID-hu model^[2].