Table 3. Computationally Predicted Oxopiperazine p53 Mimics and Their Potential to Target Mdm2.
mimetic | R1 | R2 | R3 | R4 | Kd (μM)a |
---|---|---|---|---|---|
13 | Phe | Trp | Phe | Nle | 2.5 ± 0.5 |
14 | Phe | Trp | Tyr | Leu | 3.1 ± 0.2 |
15 | Nap | Trp | Phe | Leu | 0.9 ± 0.1 |
16 | Tyr | Trp | Phe | Leu | 0.4 ± 0.05 |
17 | Tyr(O-Me) | Trp | Phe | Leu | 0.3 ± 0.01 |
18 | Phe(3-Cl) | Trp | Phe | Leu | 0.3 ± 0.04 |
19 | Phe(3-Me) | Trp | Phe | Leu | 2.6 ± 0.04 |
20 | Phe(4-Cl) | Trp | Phe | Leu | 1.3 ± 0.1 |
Binding affinity for Mdm2 as determined by a competitive fluorescence polarization assay.