TABLE 3

Summary of test data for compounds identified as correlating with ABCG2 function as measured by PhA transport

Compounds marked nontoxic were not cytotoxic at concentrations up to 100 μM. ABCG2-transfected cells were 19-fold resistant to topotecan compared to empty vector-transfected cells. Where p values were not determined, the PCC represents an average of several PCCs for different experiments with a given compound in the drug screen. Relative resistance was calculated by dividing the IC50 of each compound for the ABCG2-transfected cell line by the IC50 value for the empty vector transfected cell line. Values given are means from at least two independent experiments. Percentage inhibition of IAAP labeling of ABCG2 was determined after normalizing the value of all bands to the value obtained for IAAP incorporation into the untreated band, which was set to 100%. Values are means from two independent experiments. Increase in PhA fluorescence was determined by dividing the intracellular fluorescence of PhA in the presence of 10 μM inhibitor by the PhA fluorescence in the absence of inhibitor. Values are means from at least two independent experiments. Full chemical names for all compounds may be located at http://pubchem.ncbi.nlm.nih.gov.

CompoundPearson Correlation CoefficientP ValueRelative ResistanceIAAP Binding InhibitedPheophorbide Fluorescence
%-fold increase
NSC6367950.486.1 × 10−40.94152.4
NSC1030540.47N.D.0.33813.1
NSC305458a0.479.1 × 10−438450.99
NSC6236360.463.4 × 10−31991.1
NSC6205150.46N.D.1.1701.3
NSC6218880.46N.D.0.8601.1
NSC1073920.46N.D.47300.97
NSC1741370.463.2 × 10−40.96430.9
NSC1751500.463.8 × 10−40.8151.2
NSC3491560.453.9 × 10−437170.92
NSC6914170.447.8 × 10−40.92622
NSC6203030.441.8 × 10−30.86651
NSC6917820.449.1 × 10−41.2251.1
NSC3139810.441.9 × 10−31.2301.3
NSC2970930.431.8 × 10−31.5651
NSC2745570.404.8 × 10−31.2221.8
NSC265473a0.405.4 × 10−398791
NSC608001−0.41N.D.0.7802
NSC148958−0.434.8 × 10−4Nontoxic250.94
NSC600391b−0.445.0 × 10−4Nontoxic01.2
NSC174939−0.45N.D.0.4301.2
NSC382054−0.46N.D.2.4601.2
NSC69574−0.476.5 × 10−40.9271.3
NSC24048−0.472.7 × 10−4Nontoxic7815
NSC58368−0.503.7 × 10−4Nontoxic301
NSC45384−0.503.7 × 10−41.98512
NSC153330−0.506.1 × 10−50.92731.8

  • N.D., not determined.

  • ↵ a The IC50 value for the ABCG2 expressing line was not achieved; thus, the actual relative resistance value is likely higher.

  • ↵ b The molecular weight of this compound is not known. The compound was nontoxic up to a concentration of 100 μg/ml.