Table 5.
Summary and comparison of BRDT and BRD4 activities for JQ1 and potent compounds from DEC-Tec hits and analogs
| Compound | BRDT IC50, nM | BRDT-BD2 vs. BRDT-BD1 | BRD4 IC50, nM | BRDT-BD2 vs. BRD4-BD2 | BRD4-BD2 vs. BRD4-BD1 | t1/2,* min | |||
| BD2 | BD1 | BD2 | BD1 | MLM | HLM | ||||
| JQ1 (control) | 154 | 85 | 0.6 | 60 | 60 | 0.4 | 1 | 15 | 6 |
| 8 (CDD-1132) | 13 | >10,000† | >750 | 31 | 26,200 | 2.4 | 850 | 51 | 150 |
| 9 (CDD-1102) | 7 | 10,100 | 1,440 | 15 | 4,460 | 2.1 | 300 | 92 | 150 |
| 10 (CDD-1126) | 17 | >10,000‡ | >600 | 46 | >10,000‡ | 2.7 | >210 | 190 | 240 |
| 15 (CDD-1349) | 22 | NE§ | ∼1,000 | 140 | NE§ | 6.4 | >140 | 150 | 220 |
| 17 (CDD-1350) | 47 | 36,200 | 770 | 51 | 25,100 | 1.1 | 490 | 200 | 490 |
| 20 (CDD-1302) | 8 | 15,800 | 2,000 | 12 | 10,400 | 1.5 | 860 | 72 | 370 |
| 21 (CDD-1306) | 14 | 19,700 | 1,400 | 21 | 14,100 | 1.5 | 670 | 9 | 180 |
| 22 (CDD-1310) | 18 | 10,700 | 590 | 20 | 10,900 | 1.1 | 540 | 150 | 460 |
*
t1/2 measured using liver microsomal stability assay; assay data >60 min are an extrapolated estimate and included for relative determination of the half-life.
†
Inhibition is 11% at 10 µM for BRDT-BD1.
‡
Inhibition is 16% at 10 µM for BRDT-BD1 and 20% at 10 µM for BRD4-BD1.
§
NE: no effect at 20 µM in the AlphaScreen assay.