PF-06815345 hydrochloride is an orally active and potent inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) with an IC50 value of 13.4 μM. PF-06815345 hydrochloride significantly decreases the PCSK9 level in vivo in mouse.
PF-06815345 hydrochloride (Example 7) (1-30 μM; 5-1440 min) in human enterocyte and hepatocyte with CLint values of <82.9 μL/min/mg and 97.6 μL/min/mg, respectively[2].
PF-06815345 hydrochloride (Example 7) (100-500 mg/kg; p.o; single dose) lowers the level of PCSK9 in humanized PCSK9 mouse model. It lowers plasma PCSK9 to 72% at 500 mg/kg 4 hr later treatment[2].