Discovery of bisabosqual A, an asparagine synthetase inhibitor

November 10, 2023

Development of new anticancer drugs targeting cancer metabolism characteristics expected

A research group from Kyoto University, RIKEN CSRS, Kindai University, and Keio University has discovered a microbial metabolite bisabosqual A (Bis A), which inhibits asparagine synthetase (ASNS), showing its promising property as an anticancer drug seed for non-small cell lung cancer.

Asparagine synthetase (ASNS) is an enzyme that biosynthesizes L-asparagine (L-Asn) from L-aspartic acid (L-Asp) using L-glutamine (L-Gln) as a nitrogen source, and is the rate-limiting enzyme in the de novo synthesis of L-Asn. High expression of ASNS has been reported in lung cancer, colorectal cancer, acute lymphocytic leukemia, and other types of cancer, and has been attracting attention as a molecular target that contributes to cancer malignancy/recurrence and drug resistance. However, existing ASNS inhibitors have problems such as low cell-membrane permeability and low diversity of chemical structures. The group showed that Bis A with a novel pharmacophore exhibits remarkable anticancer activity when treated as a single agent or in combination with L-asparaginase and mTORC1 inhibitors. The results are expected to lead to development of new anticancer drugs targeting cancer metabolism characteristics.

Original article

European Journal of Pharmacology doi: 10.1016/j.ejphar.2023.176156

Y. Pan, T. Suzuki, K. Sakai, Y. Hirano, H. Ikeda, A. Hattori, N. Dohmae, K. Nishio, H. Kakeya,

"Bisabosqual A: A novel asparagine synthetase inhibitor suppressing the proliferation and migration of human non-small cell lung cancer A549 cells".

Contact

Naoshi Dohmae
Unit Leader
Biomolecular Characterization Unit