Table 2.
Prodrug stability in capan-2 cell homogenate with the presence and the absence of inhibitors.
| Half Life (min) | ||||||
|---|---|---|---|---|---|---|
| Prodrug | Phosphate Buffer pH 7.4 | Capan-2 Cell Homogenate | Cathepsin D Inhibitor | Aminopeptidase Inhibitor | TPP 2 Inhibitor | DPP 3 Inhibitor |
| 5'-O-L-leucyl-L-glycylfloxuridine | 23.1 ± 4.1 § | 3.9 ± 1.1 | 7.9 ± 0.7 | 14.0 ± 4.3 | 5.6 ± 0.6 | 32.2 ± 9.3 |
| 5'-O-L-glycyl-L-leucylfloxuridine | 35.7 ± 0.9 § | 29.2 ± 0.7 | 32.2 ± 0.1 | 33.0 ± 0.4 | 21.0 ± 0.9 | 26.5 ± 17.5 |
| 5'-O-L-valyl-L-phenylalanyl-floxuridine | 104.7 ± 7.0 § | 56.2 ±12.8 | 76.4 ±6.1 | 93.6 ± 29.3 | 46.1 ± 1.9 | 67.7 ± 15.1 |
| 5'-O-L-phenylalanyl-L-tyrosyl-floxuridine | 233.9 ± 6.6 § | 42.8 ± 0.0 | 105.7 ± 12.8 * | 54.7 ± 2.8 | 42.2 ± 1.3 | 47.2 ± 3.6 |
| 5'-O-L-phenylalanyl-L-glycyl-floxuridine | 132.1 ± 10.2 § | 4.3 ± 0.9 | 10.2 ± 3.0 | 25.7 ± 0.4 * | 19.6 ± 0.4 * | 30.1 ± 10.0 |
| 5'-O-L-phenylalanylfloxuridine | 187.0 ± 19.0 § | 3.0 ± 0.1 | 60.6 ± 4.6* | 48.7 ± 0.37 * | 15.3 ± 0.6 * | 28.9 ± 10.7 |
* <0.01; cathepsin D inhibitor–pepstatin A, aminopeptidase inhibitor–puromycin, TPP2 (tripeptidylpepptidase 2) inhibitor-H-Ala-Ala-Phe-CMK CF3CO2H, DPP3 (dipeptidylpeptidase 3)–1,10-phenanthroline. Asterisks indicate significant difference in half lives in capan-2 cell homogenate with an inhibitor to ones without inhibitors. Values presented are the mean ± s.d. (*p < 0.01; t-test). § from Reference [50].