Characterization of the potency of epidermal growth factor (EGFR)-DNA targeting combi-molecules containing a hydrolabile carbamate at the 3-position of the triazene chain.

Previous strategies for stabilizing combi-triazenes were based on masking the 1,2,3-triazene chain with a 3-acetoxymethylene group. The half-lives of the latter molecules were only ca 5 min longer than those of their parent 1,2,3-triazenes. The novel combi-molecules described herein contain a hydrolysable carbamate group that modulates their kinetics of degradation.

Design and synthesis of new stabilized combi-triazenes for targeting solid tumors expressing the epidermal growth factor receptor (EGFR) or its closest homologue HER2.

The monoalkyltriazene moiety lends itself well to the design of combi-molecules. However, due to its instability under physiological conditions, efforts were directed towards stabilizing it by grafting a hydrolysable carbamate onto the 3-position. The synthesis and biological activities of these novel N-carbamyl triazenes are described.