torcetrapib

Torcetrapib is a small molecule inhibitor of cholesteryl ester transfer protein (CETP) developed by Pfizer for the treatment of hypercholesterolemia and the prevention of cardiovascular disease. It was designed to raise 'good' HDL cholesterol and lower 'bad' LDL cholesterol by inhibiting the enzyme responsible for transferring cholesterol from HDL to VLDL or LDL. Despite achieving the desired lipid effects, Pfizer discontinued its development in December 2006 after the Phase 3 ILLUMINATE trial demonstrated a significant increase in all-cause mortality and cardiovascular events in patients receiving torcetrapib in combination with atorvastatin. The failure was linked to off-target effects, specifically the activation of the renin-angiotensin-aldosterone system, which caused elevated blood pressure and electrolyte disturbances.