Table 1 Binding affinity of compounds 1, 2, and ABBV-467 to BCL-2 family proteins, and cellular activity of ABBV-467 and other clinical-stage MCL-1 inhibitors in human tumor cell lines.
TR-FRET, Ki, nM | |||||
|---|---|---|---|---|---|
MCL-1 | BCL-2 | BCL-XL | BCL-W | BCL2-A1 | |
Binding affinity | |||||
1 (MIK665) | <0.01 | 599 | >660 | >468 | >468 |
2 | 5.54 | >1200 | >660 | NT | NT |
ABBV-467 | <0.01 | >642 | >376 | >247 | >402 |
AMO-1 EC50 (nM, 10% FBS) | H929 EC50 (nM, 10% FBS) | MV4-11 EC50 (nM, 10% FBS) | DLD-1 EC50 (nM, 10% FBS) | |
|---|---|---|---|---|
Cellular activity | ||||
ABBV-467 | 0.16 | 0.47 | 3.91 | >10,000 |
MIK665 | 2.06 | 4.75 | 10.87 | 4750 |
AMG 176 | 90.6 | 195 | 106 | >10,000 |
AZD5991 | 22.9 | 31.7 | 34.9 | >10,000 |
AMG 397 | 13.5 | 13.0 | 43.6 | >10,000 |
