MK-8262, an orally active and potent cholesteryl ester transfer protein (CETP) inhibitor (IC 50 = 53 nM, log D = 5.3), is a bistrifluoromethyl analogue that shows promise in research related to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) with potential implications for coronary heart disease (CHD).

CETP:53 nM (IC50)

MK-8262 (Compound 87) reduces cell viability in a dose-dependent manner beginning at ～10 μM in all 8 cell lines regardless of human CYP expression or glutathione depletion (HEK293/CYP cell lines expressing human CYP1A2, CYP2E1, CYP2D6, CYP2C8, CYP2B6, CYP3A4, CYP2C19, or CYP2C9)[1]. MK-8262 has no effect on human CYP protein concentration or Nrf2 activation in any of the 8 cell lines[1].

MK-8262 (Compound 87; 10 mg/kg; orally) results in a significant HDL cholesterol increase in a 2-week chronic treatment of CETP transgenic mice[1]. MK-8262 (1 mg/kg; iv) has a T 1/2 MRT of 6 hours, a CL of 2.6 mL/min?kg, and a V ss of 0.95 L/kg for mouse[1]. MK-8262 (2 mg/kg; po) has a C max of 0.43 μM and an AUC of 7.9 μM?h for mouse[1]. MK-8262 (1 mg/kg; iv) has a T 1/2 MRT of 13 hours, a CL of 3.1 mL/min?kg, and a V ss of 2.4 L/kg for mouse[1]. MK-8262 (2 mg/kg; po) has a C max of 0.4 μM and an AUC of 9.7 μM?h for mouse[1].