Table 4.
PROTACs 54–80 with the ability to degrade target proteins developed based on CRBN as E3a.
| Compd. | Target | Degradation in cell lines |
Ref. No. (Year) | |
|---|---|---|---|---|
| DC50 | Dmax (%) | |||
| 54 | BRD2/3/4 | <1 nmol/L for BRD4 | ∼100 | 200 (2015) |
| 55 | BRD2/3/4 | 430 nmol/L for BRD4 | >95 | 41 (2015) |
| 56 | BCR-ABL& c-ABL | NA | NA | 170 (2016) |
| 57 | BRD9 | NA | NA | 205 (2017) |
| 58 | CDK9 | NA | NA | 208 (2017) |
| 59 | CDK9 | NA | NA | 209 (2018) |
| 60 | CDK9 | <250 nmol/L | ∼100 | 210 (2018) |
| 61 | CDK6 | NA | NA | 212 (2018) |
| 62 | CDK4/6 | NA | NA | 213 (2019) |
| 63 | CDK4 | NA | NA | 213 (2019) |
| 64 | CDK6 | NA | NA | 213 (2019) |
| 65 | SIRT2 | 0.2–1 μmol/L | 90 | 214 (2018) |
| 66 | BRD2/3/4 | <0.03 nmol/L for BRD4 | ∼100 | 215 (2018) |
| 67 | BET | NA | ∼100 | 216 (2017) |
| 68 | BET | <0.5 nmol/L | ∼100 | 36 (2018) |
| 69 | FLT-3 | NA | NA | 217 (2018) |
| 70 | BTK | NA | NA | 217 (2018) |
| 71 | BTK | 14.6 nmol/L for wild-type BTK; 14.9 nmol/L for C481S BTK | >99 | 218 (2018) |
| 72 | BTK | ∼10 nmol/L | NA | 219 (2018) |
| 73 | ALK | 11 nmol/L for NPM-ALK | >90 | 221 (2018) |
| 59 nmol/L for EML4-ALK | ||||
| 74 | PCAF/GCN5 | 1.5 nmol/L for PCAF | 80 | 224 (2018) |
| 3 nmol/L for GCN5 | ||||
| 75 | CK2 | NA | NA | 225 (2018) |
| 76 | BCL | NA | NA | 226 (2018) |
| 77 | MDM2 | <1 nmol/L | NA | 227 (2018) |
| 78 | BTK | NA | 85 | 228 (2019) |
| 79 | BTK | 29 nmol/LM | NA | 229 (2019) |
| 80 | HDAC6 | 1.6 nmol/L | 86 | 230 (2019) |
a
DC50: the concentration at which 50% degradation was observed. Dmax: the maximal level of degradation. NA: not available.