Figure 8.

Plot of 20′ amide cLogP versus differential activity (IC₅₀ ratio) for isogenic HCT116 resistant (Pgp overexpression) and sensitive cell lines that progressively exchange in single heavy atoms or heteroatoms. The correlation defines a linear relationship between diminished resistance (ratio) that arises from reduced/abolished Pgp efflux, and a modulated physical property of the compounds (lipophilic character, cLogP) that can be predictably impacted by single atom changes. All compounds shown are more potent than vinblastine and display less resistance (vinblastine ratio = 88).