Encouraged by the successful ternary complex formation observed in vitro, H2-H4 was further studied in cells. Pleasingly, H2-H4 induced 94% degradation of pVHL30 in HEK 293 cells already after 4 hours at 1 µM and maintained pVHL30 levels at < 6% for at least 24 hours (Figure ). Subsequent dose-and time-dependent treatments (Figure and S5B) characterized H2-H4 as potent degrader of pVHL30 (DC50 = 35 nM, Dmax = 98%) inducing remarkably rapid depletion of pVHL30 (t½ = 28 min). Though performed on conceivable smallest scale, this initial DCL experiment led already to identification of a novel, potent VHL degrader through substantial amplification of this library member in the presence of a protein template.