CDK2/CycE1 is a cancer target linked to therapy resistance, and no inhibitor is reported to block formation of the complex specifically.
Isogenica selected 192 unique VHHs against CDK2, and Axxam's automated platform purified them for functional assays. Four inhibited kinase activity with two-digit nM potency, and three of those also blocked complex formation. One binder that looked inactive in the kinase assay blocked the complex instead, a result binding data alone would have missed.
Following this proof-of concept study, significantly larger VHH panels can be explored directly following selections, enabling function-first discovery for rare functional binders such as agonists.
