# Development of Cell-Permeable Adenylosuccinate Lyase Inhibitor

## TL;DR

Researchers developed a cell-permeable inhibitor for adenylosuccinate lyase, a protein linked to cancer and brain development, which could help study its role in diseases.

## Contribution

The study presents a new cell-permeable adenylosuccinate lyase inhibitor with potential for in vivo research.

## Key findings

- NF-449 fragments were synthesized to improve cell permeability.
- The compound inhibits human ADSL in HeLa cells with an IC50 of 0.4 micromolar.
- Further improvements may enable in vivo studies of ADSL.

## 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.