Table 1.

Relative toxicities of the compounds administered to mice

CompoundPtdIns-3-Kinase Inhibition IC50 (nmol/L)Cytotoxicity NCI Cell Panel IC50 (μmol/L)MTD (mg/kg)Liver Toxicity
Wortmannin1.28.93.01.00
PX-8660.12.219.50.35
PX-8671.10.518.00.23
PX-8681.011.9>30ND
PX-8701.07.16.90.94
PX-8710.110.29.00.48
PX-8802.08.1>30ND
PX-8810.80.729.50.37
PX-8820.310.218.00.92
PX-889>1021.0>30ND
PX-8901033.0300.91
  • 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.