Figure 4. Phenyl ester traceless linker editing for optimized T-API release.

a, Drug release mechanism via 1,6-elimination from triazolopyridazinium salts conjugates in T-series brush prodrugs. b, Modulation of release kinetics of the T-API via linker chemistry. c, Release of T-API inhibitor in vitro (saline buffer, 37 °C). d, Released T-API in tumors 72 h after the last dose in 60 mg/kg × 4 treatment groups (n=5). Concentration of released T-API at the tumor site is finely tuned via linker chemistry; error bars represent SD. e, Ratios of released T-API in the tumor relative to whole blood. Brush prodrugs offer favorable accumulation and differential release in the tumor. a: below limit of quantification.