PF-06649298

PF-06649298 is a small molecule inhibitor of the mammalian INDY (I’m Not Dead Yet) protein, also known as the solute carrier family 13 member 5 (SLC13A5) citrate transporter. Developed by Pfizer, this compound targets metabolic disorders by blocking the transport of extracellular citrate into cells, particularly hepatocytes. Since citrate is a critical precursor for de novo lipogenesis and a regulator of energy metabolism, its inhibition is intended to reduce hepatic fat accumulation and improve systemic insulin sensitivity. Preclinical data presented at the ADA 2022 meeting demonstrated that PF-06649298 treatment in mice with Western diet-induced non-alcoholic steatohepatitis (NASH) led to significant reductions in body weight and fat mass, improved glucose tolerance, and attenuated hepatic inflammation and steatosis. These effects were associated with the activation of the Fgf21-AMPK signaling pathway.