Recently developed several partial agonists like SR1664 and MRL24 clearly blocked the obesity-linked phosphorylation site to present the improved therapeutic index for anti-diabetic drug discovery.57 Indeed, the correlation between inhibition of this phosphorylation and the therapeutic effects in vivo suggested that it might be possible to create novel SPPARγMs which are effective for T2DM with fewer side effects.19 Consistently, we found that VSP-77 effectively reduced the Ser-273 phosphorylation level of PPARγ in a CDK5-dependent signalling assay. Here, CDK5 is linked to obesity due to melanocortin 4 receptor deficiency.