PF-06835919 (PF 06835919) is a first-in-class, potent, selective Ketohexokinase (KHK) inhibitor with IC50 of 10 nM (hKHK).
PF-06835919 showed a 6-fold higher IC50 value against human KHK-A relative to human KHK-C while inhibiting rat KHK with an IC50 of 0.21 uM.
PF-06835919 exhibited a clean off-target selectivity profile as assessed by the CEREP panel at 30 uM.
Inhibition of KHK via PF-06835919 in rats prevented hyperinsulinemia and hypertriglyceridemia from fructose feeding.
PF-06835919 reversed metabolic dysfunction as rats fed the American diet developed hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis.
