Figure 4.

Exploring the structure–activity relationship of Nectin-4/CD137 Bicycle TICAs by modulating the ratio of CD137 and Nectin-4 Bicycles. (A) Structure of four hinges used to assemble different ratios of Nectin-4/CD137 Bicycles into Bicycle TICAs. (B) EC50 and (C) E_max (fold induction over background) of Bicycle TICAs determined in HT1376/CD137 reporter coculture assay. Individual data from each experiment shown as points, geometric mean as crossbars, and number of replicates on the bottom of E_max plot. Shapes represent hinge or linker, and color represents valency of Nectin-4/CD137 Bicycles in the Bicycle TICA. The global test for significance was performed using a Kruskal–Wallis nonparametric test. Multiple pairwise tests with BCY10572 as a reference group were performed using the Mann–Whitney U test.