Relative toxicities of the compounds administered to mice
| Compound | PtdIns-3-Kinase Inhibition IC50 (nmol/L) | Cytotoxicity NCI Cell Panel IC50 (μmol/L) | MTD (mg/kg) | Liver Toxicity |
|---|---|---|---|---|
| Wortmannin | 1.2 | 8.9 | 3.0 | 1.00 |
| PX-866 | 0.1 | 2.2 | 19.5 | 0.35 |
| PX-867 | 1.1 | 0.5 | 18.0 | 0.23 |
| PX-868 | 1.0 | 11.9 | >30 | ND |
| PX-870 | 1.0 | 7.1 | 6.9 | 0.94 |
| PX-871 | 0.1 | 10.2 | 9.0 | 0.48 |
| PX-880 | 2.0 | 8.1 | >30 | ND |
| PX-881 | 0.8 | 0.7 | 29.5 | 0.37 |
| PX-882 | 0.3 | 10.2 | 18.0 | 0.92 |
| PX-889 | >10 | 21.0 | >30 | ND |
| PX-890 | 10 | 33.0 | 30 | 0.91 |
NOTE: Wortmannin and 10 semisynthetic viridins were chosen for study based on their IC50 for PtdIns-3-kinase and in the National Cancer Institute 60 human tumor cell line 3-day cytotoxicity assay. Groups of three C57BL6 mice were administered wortmannin or the semisynthetic viridins i.p. at least four doses of up to 30 mg/kg/d for 4 days. The animals were killed 24 hours after the last dose, and differential blood counts and serum chemistry were determined. The MTD is the dose that gave ≥4 g body weight loss or death of at least one of the three animals. Liver toxicity is expressed relative to wortmannin at its MTD at a dose of the viridin that gave the same myelosuppression as wortmannin at its MTD. PtdIns-3-K, PtdIns-3-kinase; NCI, National Cancer Institute; ND, could not be determined.