PCSK9 inhibitor 3f is a small molecule, orally bioavailable inhibitor of PCSK9 that antagonizes PCSK9-LDLR interaction with IC50 of 537 nM. PCSK9 inhibitor 3f shows no inhibitory activity (IC50 > 10 µM) against a small panel of kinases. PCSK9 inhibitor 3f restored LDL uptake by liver cells at sub-micromolar levels and demonstrated excellent bioavailability when delivered subcutaneously in mice. PCSK9 inhibitor 3f lowered total cholesterol levels in the plasma of wild-type mice.
