Carzelesin is a cyclopropylpyrroloindole prodrug analogue and DNA minor groove binding agent, with antineoplastic activity. Activation of carzelesin requires hydrolysis of a phenylurethane substituent to form U-76073, followed by ring closure to form the cyclopropyl-containing DNA-reactive U-76074. The formation of the DNA-reactive metabolites from carzelesin was shown to proceed very slowly in phosphate-buffered saline, but to occur rapidly in plasma from mouse, rat, dog, and human and in cell culture medium. Although carzelesin was less potent in terms of in vitro cytotoxicity and in vivo optimal dosage and showed low affinity for binding to DNA, it was therapeutically more efficacious against mouse L1210 leukemia