Given the excellent potency, rapid degradation kinetics and observed in vivo exposures of KH1 (24) we were interested to assess the potential for in vivo activity. We first looked to predict the free concentrations for elevated doses, assuming linear dose response. Assessing extent of plasma protein binding has proven challenging for bifunctional molecules due to often being very highly plasma protein bound and at the upper limits of accurate quantitation using classical assay techniques . We therefore took a dual approach, measuring plasma protein binding via a standard equilibrium dialysis assay (Supplementary Tables 1) and in addition by measuring degradation of GSK3β-HiBiT in the presence of 10% fetal calf serum or 10% mouse serum for KH1 (24) (Fig )