AbstractThe safety, pharmacokinetic, and pharmacodynamic effects of LY2584702, a selective inhibitor for p70 S6 serine/threonine protein kinase‐1, were evaluated in healthy dyslipidemic volunteers. LY2584702 was tolerated well as a monotherapy and dose‐dependently reduced low‐density lipoprotein cholesterol and triglycerides by up to 60% and 50%, respectively, without significantly changing high‐density lipoprotein cholesterol levels in plasma. LY2584702 also dose‐dependently decreased factor V activity. Alanine aminotransferase elevations were noted in 2 subjects when LY2584702 was given with atorvastatin. We suspect that the formation of 4‐aminopyrazolo[3,4‐d]pyrimidine (4‐APP) during metabolism may have contributed to some of the adverse effects of LY2584702, and the contribution of 4‐APP to the pharmacology merits further investigation. Although clinical investigation of LY2584702 has been terminated because of hepatotoxicity risk, we suggest that a selective inhibitor of p70 S6 serine/threonine protein kinase‐1 with a larger margin of safety and without the possibility of being metabolized to 4‐APP may be useful in the treatment of dyslipidemia.