Theranostics 2012; 2(2):156-178. doi:10.7150/thno.4068


Protease-Activated Drug Development

Ki Young Choi1,3, Magdalena Swierczewska1,2,3, Seulki Lee1✉, Xiaoyuan Chen1✉

1. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland, 20892, USA
2. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA
3. These authors are contributed equally.

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Choi KY, Swierczewska M, Lee S, Chen X. Protease-Activated Drug Development. Theranostics 2012; 2(2):156-178. doi:10.7150/thno.4068. Available from

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In this extensive review, we elucidate the importance of proteases and their role in drug development in various diseases with an emphasis on cancer. First, key proteases are introduced along with their function in disease progression. Next, we link these proteases as targets for the development of prodrugs and provide clinical examples of protease-activatable prodrugs. Finally, we provide significant design considerations needed for the development of the next generation protease-targeted and protease-activatable prodrugs.

Keywords: Protease, activatable probe, Alzheimer's disease, cancer, caspase, cathepsin, kallikrein, MMP, PSA, serine protease, aspartyl protease