SR 1664

Apart from direct peroxisome proliferator-activated receptor γ (PPARγ) agonism, several PPARγ ligands have recently been shown to exert anti-diabetic effects through a second, distinct biochemical function: blocking the obesity-linked phosphorylation of PPARγ by cyclin-dependent kinase 5 (Cdk5) at serine 273.¹ This effect requires binding to the PPARγ ligand binding domain, which causes a conformational change that interferes with the ability of Cdk5 to phosphorylate serine 273. SR 1664 is a small molecule that blocks phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) by cyclin-dependent kinase 5 with an IC₅₀ value of 80 nM (K_i = 28.7 nM) without exhibiting agonist activity at the PPARγ receptor.² It demonstrates potent, dose-dependent anti-diabetic effects in obese mice without inducing fluid retention and weight gain or inhibiting bone formation.²

WARNING This product is not for human or veterinary use.

1. Norris, A.W., and Sigmund, C.D. A second chance for a PPARγ targeted therapy?: A commentary on "antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation". Circ. Res. 110(1), 8-11 (2012).

2. Choi, J.H., Banks, A.S., Kamenecka, T.M., et al. Anti-diabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation. Nature 477(7365), 477-481 (2012).