In the discovery of GW5074 both an iodide and a bromide were identified as suitable substituents in the 5-position of the indolinone Treatment of Jurkat cells with bromine-substituted deltazinone-derived probe 5 reduces PDE levels in dose-and time-dependent manner (Fig. ). Up to 10 µM concentration of 5, no hook effect, which often is characteristic for bifunctional degraders, was observed . At 10 µM degrader 5 induced ca. 75 % degradation after 18 h incubation, and strong degradation was apparent already at 3 h. PDE was also degraded by 5 in HEK293T and HAP1 cell lines (Fig. ). Iodine-derivative 6 and deltasonamide-derived compound 7 also induced degradation of PDE with similar activity as displayed by compound 5 (Supplementary Fig. ).