Table 1 Optimization of SMARCA2/A4 monovalent degraders
From: Rational design of potent small-molecule SMARCA2/A4 degraders acting via the recruitment of FBXO22
Compound | SMARCA2 DC50 (nM) | SMARCA2 Dmax (%) | SMARCA4 DC50 (nM) | SMARCA4 Dmax (%) |
|---|---|---|---|---|
1 | >10,000 | -- | >10,000 | -- |
2 | 13 ± 40 | 38 ± 7.1 | 8.3 ± 2.4 | 50 ± 2.2 |
3 | 18 ± 25 | 38 ± 12 | 8.3 ± 5.3 | 43 ± 7.1 |
4 | 16 ± 6.5 | 51 ± 18 | 15 ± 9.9 | 25 ± 5.9 |
5 | 5.9 ± 2.1 | 82 ± 10 | 1.2 ± 0.75 | 99 ± 2.0 |
G-6599 (6) | 0.017 ± 0.0084 | 96 ± 2.0 | 0.057 ± 0.071 | 94 ± 3.1 |
