Oxazaphosphorine cytostatics: from serendipity to rational drug design.

On the basis of the discovery that the proapoptotic aldehyde 3-hydroxypropanal is a cyclophosphamide metabolite, a novel mechanism of action of oxazaphosphorine cytostatics is presented and confirmed by animal experiments. Furthermore, it is shown that new oxazaphosphorine cytostatics, which are on orders of magnitude more effective than already existing, can be developed on the basis of the new model for the mechanism of action.