PPARγ phosphorylation inhibitor 1 (Compound 10) is a potent PPARγ binder with the IC50 of 24 nM. PPARγ phosphorylation inhibitor 1 inhibits CDK5-mediated phosphorylation of PPARγ Ser273 with the IC50 of 160 nM. PPARγ phosphorylation inhibitor 1 displays negligible PPARγ agonism in a reporter gene assay. Antidiabetic effects[1].
PPARγ phosphorylation inhibitor 1 (compound 10) (100 μM/kg; i.g.; lean C57/BL6 mice) has a PK profile amenable to in vivo administration[1]. PPARγ phosphorylation inhibitor 1 (compound 10) (10-100 μM/kg; i.g.; daily, for 7 days) demonstrates a modest improvement of insulin sensitivity in ob/ob mice[1].
References:
[1]. Gavin O'Mahony, et al. Discovery by Virtual Screening of an Inhibitor of CDK5-Mediated PPARγ Phosphorylation. ACS Med Chem Lett. 2022 Mar 11;13(4):681-686.