Table 1.
IC50 values (nM) for compounds 1–5 in cell proliferation inhibition of RFC- and FR-expressing cell lines.
| Antifolate | hRFC | hFRα | hFRβ | hRFC/ FRα | hRFC/ FRα | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| PC43- 10 |
R2 | RT16 | RT16 (+Folic Acid) |
D4 | D4 (+Folic Acid) |
KB | KB (+Folic Acid) |
IGROV1 | IGROV1 (+Folic Acid) |
|
| 1 | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 |
| 2 | 304(89) | 448(78) | 4.1(1.6) | >1000 | 5.6(1.2) | >1000 | 1.7(0.4) | >1000 | 2.2(0.8) | >1000 |
| 3 | >1000 | >1000 | 6.3(1.6) | >1000 | 10(2.0) | >1000 | 1.9(0.7) | >1000 | 3.6(0.9) | >1000 |
| 4 | >1000 | >1000 | 54(21) | >1000 | 80(9) | >1000 | 13(7.2) | >1000 | 40(12) | >1000 |
| 5 | >1000 | >1000 | 162(18) | >1000 | 198(34) | >1000 | 23(12) | >1000 | 309(77) | >1000 |
| Methotrexate | 12(1.1) | 216(8.7) | 114(31) | 461(62) | 106(11) | 211(43) | 6.0(0.6) | 20(2.4) | 21(3.4) | 22(2.1) |
| Pemetrexed | 14(2.5) | 258(44) | 42(9) | 388(68) | 60(8) | 254(78) | 68(12) | 327(103) | 102(25) | 200(18) |
| Raltitrexed | 6.3(1.3) | >1000 | 15(5) | >1000 | 22(10) | 746(138) | 5.9(2.2) | 22(5) | 12.6(3.3) | 20(4.3) |
| Lometrexol | 12(2.3) | >1000 | 12(8) | 188(41) | 2.6(1.0) | 275(101) | 1.2(0.6) | 31(7) | 3.1(0.9) | 16(6) |
| Trimetrexate | 25(7.3) | 6.7(1.3) | 13(1) | 4.1(1) | 11(4.2) | 6.1(1.9) | 58(18) | 155(38) | 12(4) | 8.6(1.9) |
| 5a | 11(3.3) | >1000 | 277(81) | >1000 | 52(12) | >1000 | 5.8(3.5) | 32(15) | 5.2(1.7) | 6.9(1.6) |
Cytotoxicity assays were performed as described in the Experimental Section. For the FR experiments, cytotoxicity assays were performed in the absence and presence of 200 nM folic acid. The data shown are mean values from three experiments (plus/minus SEM in parentheses).