Table 1. . FLT3 kinase inhibition and antiproliferative activity of compounds.
| Entry | Compound | %FLT3 inhibition | IC50 (nM) | ||
|---|---|---|---|---|---|
| FLT3-ITD† | MV4–11 | Molm14 | Molm13-res | ||
| I | 1 | 22 | 797 | ND | ND |
| Ii | 2 | 21 | 1532 | ND | ND |
| Iii | 3 | 55 | 63 | 45.8 | 66.1 |
| Iv | 4 (HSD1169) | 80 | 5.4 | 4.9 | 5.1 |
| V | 5 | 87 | 9.1 | 16.6 | 13.7 |
| Vi | 6 | 77 | 13.7 | 26.8 | 20.7 |
| Vii | 7 | 71 | 132.5 | ND | ND |
| Viii | 8 | 53 | 38.4 | 61.5 | 40.2 |
| Ix | 9 | 54 | 61.5 | 64.1 | 86.7 |
| X | 10 | 54 | 159.4 | ND | ND |
| Xi | 11 | 21 | 744.2 | ND | ND |
| Xii | 12 | 56 | 154.5 | ND | ND |
| Xiii | 13 | 5 | >5000 | ND | ND |
| Xiv | 14 | 26 | 1449 | ND | ND |
| Xv | 15 | 6 | 1297 | ND | ND |
| Xvi | 16 | 9 | 1082 | ND | ND |
| Xvii | 17 | 19 | 772 | ND | ND |
| xviii | 18 | 20 | 484 | ND | ND |
| Xix | 19 | 8 | 898 | ND | ND |
| Xx | 20 | 27 | 1392 | ND | ND |
| Xxi | 21 | 6 | >5000 | ND | ND |
Compounds with IC50 greater than 100 nM against MV4–11 were not tested against Molm14 and Molm13-res.
†Percent inhibition was determined at 100 nM compound with 30 nM FLT3-ITD (obtained from SignalChem) in the presence of 10 μM ATP for 3 h.
ITD: Internal tandem duplication; ND: Not determined.