Figure 1. Chemical structures of brinzolamide, cholesterol prodrug, and trimethyl lock (TML) prodrug.

The hydrolysed sites of the cholesterol prodrug were located inside molecule, whereas the hydrolysed site of the TML prodrug was located at the end of the molecule. The TML substituent could easily release brinzolamide because the three methyl groups prevented the rotation of the C-C bond. Scissors indicate hydrolase enzyme.