Table 1.

Free drug in vitro properties

Cytotoxicitya, relative tubulin binding affinity, and stability
% Intact at 48 hours, 37°C
CompoundDrugL540cy, HLL428b, HLHL60, AMLHL60/RVb, AMLTubulin RBAcCell mediaMouse plasma
3Tub(OAc)0.14 nmol/L0.0390.151.01.046%54%
4Tub(OH)196211>1,000NCdNANA
5Tub(OEt)0.0860.130.0935.80.89100%100%
6Tub(OiVal)0.0620.110.0455.80.2692%91%
  • aFollowing 96 hours treatment, cells were assessed for viability as described in the Materials and Methods.

  • bMDR-positive by rhodamine efflux.

  • cBiochemical potency: tubulin RBA = ratio of Tub(OAc) EC50/Tub analogue EC50.

  • dNC, noncompetitive.