Table 3.
Enzyme Inhibition and Whole Cell Data of Ethylenediamine-Based FTIs Exhibiting a Range of R3 Sulfonamides
 | ||||||
|---|---|---|---|---|---|---|
| Compound | IC50 (nM) | Selectivity | Processing IC50 (μM) | |||
| Number | R3 | hFTase | GGTase-I | H-Ras | Rap1A | |
|
1aa (FTI-2630) |
|
720 ± 200 | >10,000 | >14 | 6 (n = 2) | >10 |
|
1ab (FTI-2600) |
|
54 ± 30 | >10,000 | >14 | >10 | >10 |
|
1ac (FTI-2506) |
|
114 ± 80 | 600 ± 300 | 5.3 | >10 | >10 |
|
1ad (FTI-2611) |
|
180 ± 100 | 5500 ± 1900 | 31 | 5.7 ± 1.5 | >10 |
|
1ae (FTI-2607) |
|
1400 ±900 | >10,000 | 7.1 | >10 | >10 |
|
1a (FTI-2585) |
|
56 ± 29 | 2700 ± 2200 | 48 | 1.9 ± 1.2 | >10 |
|
1af (FTI-2601) |
|
72 ± 20 | >10,000 | >139 | >10 | >10 |
|
1ag (FTI-2602) |
|
30 ± 33 | 510 ± 270 | 17 | 4.3 ± 1.5 | >10 |
|
1ah (FTI-2635) |
|
320 ± 190 | 6100 ± 1600 | 19 | 0.65 (n = 2) | >10 |
|
1ai (FTI-2536) |
|
67 ± 38 | 940 ± 20 | 14 | 0.4 (n = 2) | >10 |
|
1aj (FTI-2538) |
|
870 ± 120 | 13,400 (n = 2) | 15 | 0.8 (n = 2) | >10 |
|
1ak (FTI-2639) |
|
2300 ± 1500 | 5900 ± 3000 | 2.6 | 0.4 (n = 2) | >10 |
|
1a (FTI-2533) |
|
510 ± 460 | 1360 ± 740 | 2.7 | >10 | >10 |
|
1am (FTI-2637) |
|
6200 ± 920 | >10,000 | >1.6 | >10 | >10 |
|
1an (FTI-2542) |
|
5300 ± 1700 | >10,000 | >1.9 | ND | ND |
|
1ao (FTI-2614) |
|
51 ± 26 | 780 ± 320 | 15 | 1 ± 0 | >10 |
|
1ap (FTI-2615) |
|
54 ± 30 | 630 ± 240 | 12 | 0.3 ± 0.2 | >10 |
|
1aq (FTI-2623) |
|
370 ± 210 | 580 ± 200 | 1.6 | 2 ± 1 | >10 |
|
1ar (FTI-2624) |
|
78 ± 12 | ND | - | 5 ± 3 | >10 |
|
1as (FTI-2625) |
|
370 ± 370 | 6500 ± 2900 | 18 | >10 | >10 |
|
1at (FTI-2610) |
|
230 ± 150 | 550 ± 120 | 2.4 | 3 ± 0 | >10 |
|
1au (FTI-2612) |
|
1700 ± 900 | 7300 ± 2200 | 4.3 | 5 ± 1 | >10 |
|
1av (FTI-2715) |
|
390 ± 100 | 5800 ± 3500 | 15 | 4 ± 1 | >10 |
|
1aw (FTI-2631) |
|
590 ± 300 | >10,000 | >17 | >10 | >10 |
|
1ax (FTI-2602) |
|
60 ± 10 | 530 ± 120 | 8.8 | 0.1 ± 0.07 | >10 |
|
1ay (FTI-2670) |
|
3700 ± 790 |
>10,000 | >2.7 | >2 | >2 |
|
1az (FTI-2722) |
|
510 ± 62 |
>10,000 | >20 | >10 | >10 |