A library of duocarmycin bioprecursors based on the CPI and CBI scaffolds were synthesized and used to probe selective activation by cells expressing CYP1A1, 1B1 and 2W1, CYPs known to be expressed in high frequency in some tumors. Several CPI-based compounds were pM-nM cytotoxic in CYP1A1 expressing cells while CYP1B1 was not capable of activating these duocarmycin analogues. CYP2W1 was also shown to sensitize proliferating cells to several compounds demonstrating its potential as a target for tumor selective activation of duocarmycin bioprecursors.