TABLE 5

Effects of CES inhibitors on 5′-DFCR formation in the combination of human liver microsomes and cytosol, microsomes, and cytosol Capecitabine (100 μM) was incubated with the combination of microsomes (0.5 mg/ml) and cytosol (2.5 mg/ml), microsomes (0.5 mg/ml), and cytosol (2.5 mg/ml) obtained from BD Gentest in the presence or absence of the CES inhibitor. BNPP and DFP concentrations ranged from 0.1 to 10 μM and 5 nM to 1.0 μM, respectively. The incubation contained the inhibitor mixture of 500 μM THU, 0.1 μM TPI, and 100 μM CDHP. Each data point represents the mean of duplicate determinations. Values in parentheses indicate the percentages of the control activities.


Inhibitor


5′-DFCR Formation

IC50

Microsomes + Cytosol
Microsomes
Cytosol
Microsomes + Cytosol
Microsomes
Cytosol
μM pmol/min/mg protein nM
None 3.0 (100) 6.2 (100) 1.9 (100)
BNPP 0.1 2.4 (78) 5.7 (92) 1.5 (82) 609 1064 381
1 1.1 (35) 3.3 (52) 0.6 (34)
10 0.0 (0) 0.5 (7) 0.0 (0)
DFP 0.05 2.8 (94) 5.6 (90) 1.4 (74) 158 115 77
0.1 2.0 (67) 3.5 (56) 0.7 (38)

1
0.0 (0)
1.2 (18)
0.4 (23)