GW610

1. 5F203 IH352 GW610 Active in breast and not colon cell lines Active in colon and breast cell lines Active in colon and breast cell lines Activity dependent on CYP1A1 – (but not in HCC 2998 colon cell line which has some sensitivity unrelated to CYP1A1) Activity not dependent on CYP1A1 Activity not dependent on CYP1A1 A ligand for the AhR Likely to be a ligand for the AhR Likely to be a ligand for the AhR Removal of fluorine does not affect activity Movement/removal of fluorine or movement/removal of methoxy groups abolishes activity Insoluble in water Solubility unknown – but has the potential to be turned into a prodrug form similarly to 5F203 Soluble as a prodrug (Phortress) Causes S phase block in colon cells only, no significant impact on cell cycle of breast cell lines Causes S phase block Causes a G2/M block in both sensitive and resistant cell lines Causes DNA adducts in sensitive cell lines only Causes DNA adducts in sensitive cell lines only Causes DNA adducts in sensitive cell lines only 2 sensitive breast and cell lines acquired resistance after prolonged drug treatment. These cell lines are sensitive to GW610 2 sensitive breast and colon cell lines acquired resistance after prolonged drug treatment. These cell lines are also resistant to 203 Activity appears unrelated to COX-2, NAG-1 and PPAR gamma NAG-1 (NSAID activated gene) induced in MCF-7 cells Activity appears unrelated to COX-2, NAG-1 and PPAR gamma 203 resistant cell lines have increased CYP1B1 gene expression COMPARE analysis shows GW610 is novel