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Design, Synthesis and Evaluation of AdSS Bisubstrate Inhibitors
Nidhi Tibrewal1, Gregory I Elliott1,2,3
1Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0596, USA.
Abstract:
Many cancers lack the expression of methylthioadenosine phosphorylase (MTAP). These cancers require adenylosuccinate synthetase (AdSS) for nucleic acid synthesis. By inhibiting adenylosuccinate synthetase, we potentially have a new therapeutic agent. Bisubstrate inhibitors were synthesized and evaluated against purified AdSS. The best activity was obtained with adenosine bearing a four-carbon linker that connects the N-formyl-N-hydroxy moiety to the 6-position of the purine nucleoside.
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