2. Academic Validation
  3. Development of Cell-Permeable Adenylosuccinate Lyase Inhibitor

Development of Cell-Permeable Adenylosuccinate Lyase Inhibitor

  • Methods Protoc. 2025 Oct 29;8(6):126. doi: 10.3390/mps8060126.
Yijia Hu 1 2,  Young-Sam Lee 1 3
Affiliations

Affiliations

  • 1 Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • 2 Department of Family Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
  • 3 Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
PMID: 41283386 DOI: 10.3390/mps8060126
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 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.

Keywords

adenylosuccinate lyase; inhibitor; nucleotide; screening.

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