Table 4. Inhibition for CES Mediated Hydrolysis Reactionsa.
| inhibitor | main human enzyme | IC50 | Ki | references | IC50 or extent of inhibition (this study) |
|---|---|---|---|---|---|
| PMSF | most esterases | 0.541 mM | 0.56 mM | (47, 48, and 54) | NPA: ∼200 μM in pig cornea |
| digitonin | CES1 | 9.2 ± 0.4 μM (rhCES1) | NA | (54 and 55) | NPA: 38 ± 3 μM in pig cornea |
| 25.8 μM (rhCES1) | DME: >200 μM in pig cornea, ∼30% at 200 μM in rabbit cornea, <20% in both conjunctivas | ||||
| timolol | CES2 | 20% inhibition at 200 μM | NA | (2, 54, and 55) | NPA: no inhibition in pig cornea |
| FDA: <20% inhibition in rabbit retina, no inhibition in pig retina | |||||
| verapamil | CES2 > CES1 | 7.94 μM (rhCES2) | 11.5 ± 1.20 μM (HLM) | (20, 54, and 65) | NPA: 28 ± 7 μM in pig cornea; |
| 3.84 ± 0.99 μM (rhCES2) | FDA: 38 ± 8 μM in rabbit retina, no inhibition in pig retina | ||||
| diltiazem | CES2 > CES1 | 3.98 μM (rhCES2) | 2.89 ± 0.39 μM (HLM) | (20, 54, and 65) | NPA: no inhibition in pig cornea |
| 0.25 ± 0.02 μM (rhCES2) |
a
HLM, human liver microsomes; NA, not available; rhCES, recombinant human CES1 or CES2. Inhibition of substrate hydrolysis was done in pig cornea for NPA, in pig and rabbit cornea and conjunctiva for DME, and in pig and rabbit retina for FDA.