SMAD3 and chronic kidney disease: Knowing that HIF-2α plays a strong reno-protective role in the progression of chronic kidney disease, and protein von Hippel–Lindau (VHL) is a HIF specific E3 ligase [4], we hypothesized that a new PROTAC, connected this Smad3-binding SMC and a VHL-binding SMC with a linker, might have two effects at one time: the degradation of Smad3 as well as the stabilization of HIF-2α (Fig. 1A).