Table 1.
Efficacies of Small-Molecule Inhibitors of Bcl-2
| Small-Molecule Inhibitor | IC50 Range (μM)* | Binding Coefficients†
|
Reported Range In Vivo
|
Studies (first author) | |||
|---|---|---|---|---|---|---|---|
| Bcl-2 | Bcl-xL | Mcl-1 | Therapeutic | MTD (mg/kg qd) | |||
| Gossypol | 2.2-13.2 | 0.28-50 | 0.4-3.03 | 1.75 | 5-30 mg/kg | 3 × 40 | Kitada,49 Zhang,50 Mohammad,51 Wolter,52 Bauer,29 Xu,53 Zeitlin,55 Van Poznak57 |
| HA14-1 | 5-20 | 0.9-100 | NA | NA | 400 nmol (approximately 136 μg)/mouse | NA | van Delft,7 Wang,54 Lickliter,56 Chen,58 Manero59 |
| TW-37 | 0.2-0.29 | 0.12-0.7 | 1.11 | 0.26 | 3-30 mg/kg qd | 3 × 40 | Wang,60 Mohammad,61 Zeitlin,55 Verhaegen62 |
| GX15-070 | 1.7 | 1.11‡ | 4.69‡ | 2.9‡ | 0.25-3 mg/kg/d iv | NA | Zhai,43 Campàs,63 Nguyen64 |
| ABT-737 | 0.13-5 | 0.12 | 0.064 | > 20 | 20-100 mg/kg/ip qd | NA | van Delft,7 Oltersdorf,30 Konopleva,65 Zhai43 |
| EGCG | 20-65 | 0.45 | 0.59 | 0.92 | 1.5 mg/d ip | NA | Yang,45 Pan,46 Navarro-Perán,47 Jung48 |
| Antimycin A and derivatives | 0.37-0.7 | 0.82-100 | 2.7 | 2.51 | 2 mg/kg ip | NA | van Delft,7 Zhai,43 Tzung,66 Manion,67 Kim,68 Cao,69 Guichard70 |
NOTE. Values are representative ranges of activities for drugs in a variety of cells and conditions. Lack of consistent and comparable studies between various compounds makes more exact reporting of values difficult to interpret.
Abbreviations: IC50, half maximal inhibitory concentration; MTD, maximum-tolerated dose; qd, each day; NA, not available at time of writing; iv, intravenously; ip, intraperitoneally.
*
Refers to reported IC50, half maximal effective concentration (EC50), or median lethal dose (LD50).
†
Determined using varying competitive binding assays.
‡
Data for GX15, derivative of clinically tested GX15-070.