Design,Synthesis and Evaluation of AdSS Bisubstrate Inhibitors |
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Authors: | Nidhi Tibrewal Dr. Gregory I. Elliott |
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Affiliation: | Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0596 USA |
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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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Keywords: | adenylosuccinate synthetase lung cancer methylthioadenosine phosphorylase small molecules |
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