Table 1.
Effects of AR antagonists on AR wild type and W742C/L mutants in cell‐based transactivation assays
| Compound | R1881 (nM) | AR wild type | AR W742C | AR W742L |
|---|---|---|---|---|
| Darolutamide | 0.1 | 80 ± 103 | 170 ± 701,3 | 200 ± 301,2,3 |
| 1 | 460 ± 201,2,3 | 700 ± 2901,2,3 | 860 ± 1801,2,3 | |
| 10 | 6,560 ± 1,430 | 7,530 ± 2,3603 | 9,400 ± 7803 | |
| (S,R)‐darolutamide | 0.1 | 60 ± 101,2,3 | 120 ± 201,3 | 190 ± 801,2,3 |
| 1 | 400 ± 801,2,3 | 490 ± 1101,2,3 | 1,110 ± 2201,2,3 | |
| 10 | 5,880 ± 2,920 | 6,800 ± 1,8603 | 9,400 ± 7803 | |
| (S,S)‐darolutamide | 0.1 | 100 ± 30 | 210 ± 601,3 | 290 ± 1401,3 |
| 1 | 650 ± 120 | 750 ± 1401,2,3 | 1,420 ± 2201,3 | |
| 10 | 7,560 ± 2,430 | 8,570 ± 1,7601,2,3 | >10,000 | |
| Keto‐darolutamide | 0.1 | 80 ± 203 | 160 ± 101,3 | 300 ± 301,2,3 |
| 1 | 510 ± 901,2,3 | 600 ± 6801,2,3 | 1,250 ± 2501,3 | |
| 10 | 5,670 ± 1,8203 | 5,140 ± 1,1501,2,3 | 8,760 ± 2,1403 | |
| Enzalutamide | 0.1 | 100 ± 10 | 530 ± 150 | 1,350 ± 390 |
| 1 | 740 ± 40 | 3,530 ± 1,630 | 7,460 ± 2,200 | |
| 10 | 8,450 ± 1,570 | >10,000 | >10,000 | |
| Apalutamide | 0.1 | 90 ± 10 | 200 ± 160 | 590 ± 130 |
| 1 | 710 ± 80 | 1,560 ± 220 | 3,380 ± 1,780 | |
| 10 | 8,290 ± 1,600 | >10,000 | >10,000 | |
| Bicalutamide | 0.1 | 240 ± 90 | Agonism | Agonism |
| 1 | 2,330 ± 750 | 90 ± 10% | 100 ± 10% | |
| 10 | >10,000 |
Notes: Mean IC50 ± SD values for at least three biological replicates are given in nM. Cells were treated with the indicated R1881 concentrations (in nM) and the mentioned AR antagonist. In some cases agonism was found and the % activity measured in the presence of 1 μM compound, in comparison to 1 nM R1881 which was set to 100%, is given in bold. Statistical analysis was performed with t‐test on average pIC50 values. Superscripts indicate antagonism significantly stronger compared to enzalutamide1, apalutamide2 or bicalutamide3.