Table 2. Bcl-xL degraders designed with various linkages and substituted positions to thalidomide/lenalidomide.
| |||||||
|---|---|---|---|---|---|---|---|
| X | Substitution position | Cmpd | L | IC50a (nM) | Cmpd | L | IC50a (nM) |
| ABT-263 | — | 202.3 | XZ739 | — | 10.1 | ||
| CO | C4- | 2a |
|
10.4 | 2d |
|
10.6 |
| 2b |
|
5.2 | 2e |
|
36.1 | ||
| 2c |
|
6.2 | 2f |
|
45.5 | ||
| C5- | 3a |
|
14.3 | 3b |
|
4.3 | |
| CH2 | C4- | 4a |
|
4.1 | 4b |
|
4.5 |
| C5- | 5a |
|
2.1 | 5b (PZ671) |
|
1.3 | |
a
IC50 values are the means of at least three independent experiments; MOLT-4 cells were treated for 48 h.