July 11, 2025
Kyoto University
Institute of Science Tokyo
RIKEN
Keio University
A research group including Professor Hideaki Kakeya and doctoral student Lei Zhang of the Graduate School of Pharmaceutical Sciences at Kyoto University; Professor Hidehiro Uekusa of the Department of Chemistry, School of Science at the Institute of Science Tokyo; Naoshi Dohmae, Unit Leader at the RIKEN Center for Sustainable Resource Science; and Hidenori Hirano, Project Associate Professor at the Graduate School of Science and Technology, Keio University, has discovered new compounds, stachybenzals A–C, produced by a filamentous fungus of the genus *Stachybotrys*. These compounds act as novel covalent asparagine synthetase (ASNS) inhibitors, and the group has demonstrated their promise as lead compounds for anticancer drugs against non-small cell lung cancer.
Asparagine synthetase (ASNS) is the rate-limiting enzyme in the de novo synthesis of L-asparagine (L-Asn). It biosynthesizes L-Asn from L-aspartic acid (L-Asp) using L-glutamine (L-Gln) as a nitrogen source. High expression of ASNS has been reported in cancers such as lung cancer, colorectal cancer, and acute lymphoblastic leukemia, where it contributes to malignancy, recurrence, and resistance to anticancer drugs. To develop covalent ASNS inhibitors, the research group established a simple and highly sensitive screening system using the lysine residue-mimicking compound N-Boc-L-Lys and discovered stachybenzals A–C, novel meroterpenoid compounds produced by a filamentous fungus of the genus *Stachybotrys*. They revealed that these compounds inhibit enzyme activity and exhibit anticancer activity by covalently binding to the lysine residue at position 556 of ASNS. This discovery is expected to lead to the development of new anticancer drugs that target cancer metabolic characteristics.
The results of this research were published online in the international academic journal Journal of Natural Products on July 10, 2025.
For the full press release, please see below.