5-(4-氯苯基)-1-(4-甲氧基苯基)-3-(三氟甲基)-1H-吡唑

Preincubation of COX-1 with SC-560 inhibits the conversion of arachidonic acid to PGE2 in a concentration-dependent manner. The IC ₅₀ of SC-560 for COX-2 is 6.3 μM, nearly 1,000-fold higher than with COX-1. SC-560 shows a dose and time dependent inhibitory effect on HCC cell growth. SC-560 also inhibits colony formation in soft agar and induces apoptosis in HCC cells in a dose-dependent manner. Moreover, SC-560 decreases the levels of the anti-apoptotic proteins survivin and XIAP and activates caspase 3 and 7 in a dose and time dependent fashion.

Oral dosing with either 10 or 30 mg/kg SC-560 1 hour before assay completely inhibits ionophore-stimulated TxB2production, indicating that SC-560 is orally bioavailable and inhibits COX-1 in vivo . SC-560 extensively distributes into rat tissues, and has a CL approaching hepatic plasma flow. The drug displays low less than 15% and formulation dependent bioavailability after oral administration and demonstrates kidney toxicity.