November 10, 2023
Kyoto University
RIKEN
Keio University
A research group, including Professor Hideaki Kakeya and doctoral student Yanjun Pan from the Graduate School of Pharmaceutical Sciences at Kyoto University, Unit Leader Naoshi Dohmae from the RIKEN Center for Sustainable Resource Science, Professor Kazuto Nishio from the School of Medicine at Kindai University, and Project Associate Professor Hidenori Hirano from the Graduate School of Science and Technology at Keio University, has discovered Bisabosqual A (Bis A), a microbial metabolite that inhibits asparagine synthetase (ASNS), and has demonstrated its promise as a lead compound 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), biosynthesizing 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 lung cancer, colorectal cancer, and acute lymphoblastic leukemia, and it is attracting attention as a molecular target that contributes to cancer malignancy, recurrence, and drug resistance. However, existing ASNS inhibitors have issues such as low cell membrane permeability and a lack of chemical structural diversity. This research group has revealed that Bis A, which possesses a novel pharmacophore, exhibits significant anticancer activity when administered as a monotherapy or in combination with L-asparaginase or mTORC1 inhibitors. This is expected to lead to the development of new anticancer drugs that target the metabolic characteristics of cancer.
This research was published online in European Journal of Pharmacology on October 30, 2023.
Please see below for the full press release.