TABLE 1

In vitro potencies of SK inhibitors against the JC cell line compared with both blood and tumor inhibitor concentrations The potencies of each SK inhibitor toward murine JC cells were determined using the sulforhodamine binding assay. (GST-hSK-1 inhibition data are provided for comparison.) Data represent the concentrations required to inhibit cell survival by 50% and are the mean ± S.D. of triplicate experiments. At the end of the i.p. tumor study outlined in Fig. 5 or in typical tumor-bearing mice, animals were i.p. dosed with an SK inhibitor and euthanized 1 h later. Blood and tumor samples were analyzed for SK inhibitor concentrations. Values represent the mean ± S.D. of each treatment group (n = 5).


Inhibitor

GST-hSK-Ia

JC Cytotoxicity

Cblood 1 h

Ctumor 1 h
μM μM μM nmol/g
SKI-I 1.1 ± 0.3 0.9 ± 0.3 5.9 ± 3.3 8.7 ± 11.9
SKI-II 0.5 ± 0.3 1.1 ± 0.3 3.5 ± 4.9 30.5 ± 43.6
SKI-V
2.0 ± 0.2
0.9 ± 0.1
2.4 ± 2.1
0.4 ± 0.2