PF-06446846 hydrochloride is an orally active, highly selective translation inhibitor of the proprotein convertase subtilisin/kexin type 9 (PCSK9). It inhibits PCSK9 by inducing ribosome parking around codon 34.
PF-06446846 inhibits the secretion of PCSK9 by Huh7 cells with an IC 50 of 0.3 μM.
PF-06446846 (oral gavage; 5-50 mg/kg/day for 14 days) lowers plasma PCSK9 in a dose-dependent manner and lowers total cholesterol levels.
Male Sprague-Dawley (Crl:CD [SD] rats, 6-8 wk old at initiation of dosing)
5, 15, and 50 mg/kg
Oral gavage; daily for 14 days
Lowered plasma PCSK9 in a dose-dependent manner and lowered total cholesterol levels.