Table 3.
Properties of PTEFb inhibitors BAY‐958, benzyl sulfone 4, and BAY 1143572.
| BAY‐958 | 4 | BAY 1143572 | |
|---|---|---|---|
| CDK9/CycT1 IC50 [nm] | 11 | 24 | 13 |
| Selectivity vs. CDK2, ratio of IC50 values | 98 | 67 | 100 |
| HeLa IC50 [nm][a] | 1000 | 1500 | 920 |
| MOLM‐13 IC50 [nm][a] | 280 | 130 | 310 |
| TPSA[b] | 120.0 | 94.1 | 100.9 |
| Sw, pH 6.5 [mg L−1][c] | 11 | 4 | 479 |
| P app A→B [nm s−1] | 22 | 143 | 35 |
| Efflux ratio | 15 | 1.2 | 6 |
| CLb, ratHep [L h−1 kg−1] | 0.33 | 0.79 | 0.17 |
| CLb, ratLM [L h−1 kg−1] | 0.48 | 0.58 | 0.15 |
| CLb, rat in vivo, i.v. [L h−1 kg−1] | 0.50 | 2.7 | 1.1 |
| V ss, rat in vivo, i.v. [L kg−1] | 1.4 | 1.5 | 1.0 |
| t 1/2, rat in vivo, i.v. [h] | 0.7 | 0.3 | 0.6 |
| AUC,[d] rat in vivo, p.o. [mg h−1 L−1] | 0.11 | 0.16 | 0.28 |
| C max,[d] rat in vivo, p.o. [mg L−1] | 0.029 | 0.059 | 0.058 |
| F, rat in vivo, p.o. [%] | 10 | 53 | 54 |
| Blood/plasma ratio (rat) | 3.0 | 1.2 | 1.1 |
| CYP inhibition [μm] | >20 | >20 | >20 |
| CYP1A2 induction | NOEL[e] ≤5 μg L−1 | no (up to 370 μg L−1) | no (up to 370 μg L−1) |
[a] Cells were treated with test compounds for 96 h. [b] Topological polar surface area.20 [c] The solid state of the test compounds was not characterized. [d] Normalized to 1 mg kg−1. [e] No‐observed‐effect‐level.