Table IV.
PK and PD of Nonsteroidal Androgen Receptor Agonists
| ID | Compound structure | RBAa (%) |
Orally available |
In vivo half life |
|---|---|---|---|---|
| Testosterone |  |
28 (73) | No | <30 min |
| LG121071 |  |
18 (48) | Yes | N/A |
| LGD2226 |  |
170 (77) | Yes | N/A |
| S4 |  |
6 (52) | F = 1 (rat) (58) (10 mg/kg) | 4 h (rat) (58) 4 h (human) |
| S1 |  |
4 (52) | F = 0.6 (rat) (57) (10 mg/kg) | 4 h (rat) (57) |
| C6 |  |
11 (56) | F = 0.8 (rat) (56) (10 mg/kg) | 6 h (rat) (56) |
| S22 |  |
6 (57) | Yes | 6 h (rat) (57) |
| BMS 564929 |  |
3 (67) | Yes | 8Y14 h (human) |
| S-40503 |  |
0.3 (68) | Yes | N/A |
| Castrated rat modelb | |||
|---|---|---|---|
| Prostate | L.A. | Bone | LH/FSH |
| ED50 = 0.5 mg/kg Emax = 120% (52) | ED50 = 0.6 mg/kg Emax = 104% (52) | Full agonist | ID50 = 0.26 mg/kg (67) |
| N/A | N/A | N/A | ↓ LH to intact level @ 20 mg/kg, po (48) |
| 100% intact level @ 100 mg/kg | 100% intact level @ 3 mg/kg | Full agonist (49) | N/A |
| ED50 = 1.6 mg/kg Emax = 35% (52) | ED50 = 0.6 mg/kg Emax = 101% (52) | Full agonist (55) | Partial agonist (52) |
| ED50 = 1.7 mg/kg Emax = 15% (52) | ED50 = 1.6 mg/kg Emax = 75% (52) | N/A | Partial agonist (52) |
| ED50 = 3.9 mg/kg Emax = 130% (56) | ED50 = 0.85 mg/kg Emax = 130% (56) | N/A | ↓ LH to intact level @ 1.5 mg/kg (56) |
| ED50 = 0.5 mg/kg Emax = 51% (57) | ED50 = 0.12 mg/kg Emax = 136% (57) | Full agonist | N/A |
| ED50 = 141 μg/kg Emax = 105% (67) | ED50 = 0.9 μg/kg Emax = 120% (67) | N/A | ID50 = 8 μg/kg (67) |
| 80% intact level @ 30 mg/kg | 115% intact level @ 30 mg/kg | Full agonist | N/A |
a
RBA: Relative binding affinity compared to DHT.
b
All reagents were administered via daily subcutaneous injections unless noted otherwise.