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Methods Protoc., Volume 8, Issue 6 (December 2025) – 1 article

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Communication
Development of Cell-Permeable Adenylosuccinate Lyase Inhibitor
by Yijia Hu and Young-Sam Lee
Methods Protoc. 2025, 8(6), 126; https://doi.org/10.3390/mps8060126 (registering DOI) - 29 Oct 2025
Abstract
Abnormal adenylosuccinate lyase (ADSL) activity is associated with cancer and neurodevelopmental processes. However, a cell-permeable ADSL inhibitor is not yet available. Our high-throughput screen identified NF-449 as a potential lead compound. To improve cell permeability of the lead compound, fragments of NF-449 were [...] Read more.
Abnormal adenylosuccinate lyase (ADSL) activity is associated with cancer and neurodevelopmental processes. However, a cell-permeable ADSL inhibitor is not yet available. Our high-throughput screen identified NF-449 as a potential lead compound. To improve cell permeability of the lead compound, fragments of NF-449 were synthesized. This fragment, 2,2’-(1,3-phenylenebis(carbonylimino))-bisbenzenesulfonate, competitively inhibits purified human ADSL with an inhibitory constant of 0.4 micromolar. Its triethylammonium salt inhibited ADSL in HeLa cells with an IC50 of 0.4 micromolar. While this compound might not be ready for in vivo applications yet, further improvement in its permeability might produce useful reagents for in vivo studies of ADSL. Full article
(This article belongs to the Section Molecular and Cellular Biology)
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