Table 2

Activity of CB300638 and CB3717 in human A431 and A431-FBP cell lines in 20 nm and 1 nm folate (R,S LV)

The A431-FBP cell line has been transfected with human α-FR, and the A431 cells have been transfected with the empty vector. Cells were cultured in folate-free DMEM (supplemented with 20 nm or 1 nm R,S-LV) and dialysed FCS. IC50 values are given in the presence and absence of 1 μm FA. Growth inhibition was measured by an MTT assay after 72 h (A431) and 96 h (A431-FBP) equivalent to approximately four control cell doublings.

Inhibition of cell growth, IC50, μmInhibition of cell growth, IC50, μm
A431A431 + 1 μm FAA431-FBPA431-FBP + 1 μm FA
(RFC+/FBP−)(RFC+/FBP++)
CB3717
 20 nm LV1.3 ± 0.641.4 ± 0.560.25 ± 0.11 a(5)0.45 ± 0.14 b(2)
 1 nm LV0.60 ± 0.370.94 ± 0.760.0038 ± 0.0029 a(160)0.26 ± 0.023 b(68)
CB300638
 20 nm LV0.81 ± 0.360.97 ± 0.580.0028 ± 0.0020 (290)0.49 ± 0.17 (180)
 1 nm LV0.67 ± 0.240.81 ± 0.550.0021 ± 0.0010 (320)0.49 ± 0.13 (230)
  • a IC50 A431/IC50 A431-FBP.

  • b Fold increase in IC50 in the presence of 1 μm folic acid.