Table 1.

Cytotoxicity of Genz-644282 in camptothecin-resistant human cancer cell lines

CompoundParental cell line, IC50, nmol/LaResistant subline, IC50, nmol/LResistance ratiobMechanism of resistance (ref)
DU145 prostate cancerRC0.1Mutant Top1 (23, 24)
camptothecin11.5 ± 6.4>1,000>87
Genz-6442824.8 ± 0.3606.3 ± 456.7126
CCRF-CEM leukemiaCCRF-CEM C2Mutant Top1 (25, 26)
camptothecin5.5>1,000>182
Genz-6442825.4 ± 1.89.31.7
MCF7 breast cancerMCF7-siTop1siRNA Top1 (22)
camptothecin13.3 ± 2.139.83
Genz-6442822.8 ± 0.15.9 ± 0.12.1
HCT116 colon cancerHCT116-siTop1siRNA Top1 (22)
camptothecin14.3 ± 5.036.8 ± 0.62.6
Genz-6442829 ± 0.111.9 ± 2.71.3
H460 NSCLCH460/MitoMitoxantrone treated (ABCG2 overexpresser)
topotecan175.5 ± 139.2>767 ± 403>4.4
Genz-64428215.8 ± 14.7>678 ± 558>43
KB3.1 cervical cancerKB3.1/VinblVinblastine treated (ABCB1 overexpresser)
Doxorubicin86.7 ± 15.7>1,000>11.5
Genz-64428267.6 ± 15.1314 ± 129.64.6

Abbreviation: CPT, camptothecin.

  • aIC50 (concentration of drug required for 50% cell growth inhibition) and relative resistances to Genz-644282 and the appropriate positive control (camptothecin, topotecan, or doxorubicin) in 6 different pairs of matched cell lines. Individual values correspond to independent experiments.

  • bRelative resistance was calculated by dividing the IC50 of the mutant cell line by the IC50 of the corresponding parental cell line.