Identification of a candidate PRODH allosteric inhibitor MBTP-15324: modulation of proline metabolite profiles and ECM-associated gene-expression changes in lung cancer cells.

Authors

Yuxuan Zhou, Dingyuan Bai, Zhihan Li, Ciqin Li, Chunqiong Li, Mengyao Chen, Cheng Guo, Jun Yan, Yonglong Han, Quanjun Yang

Published in

Journal of enzyme inhibition and medicinal chemistry. Volume 41. Issue 1. Pages 2719719. Epub Aug 24, 2026.

Abstract

Current proline dehydrogenase (PRODH) inhibitors lack scaffold diversity. Through virtual screening, microscale thermophoresis, and molecular dynamics simulations, we identified MBTP-15324 as a candidate novel PRODH allosteric inhibitor (Kd = 1.45 μM). In PRODH-overexpressing lung cancer cells (A549 and LLC), MBTP-15324 significantly attenuated cell viability, colony formation, and migration. Furthermore, multi-omics analyses revealed that this putative inhibitor partially reversed arginine-proline metabolic dysregulation and downregulated transcriptional programs associated with inflammation, cell adhesion, and the extracellular matrix (ECM). In conclusion, MBTP-15324 provides a novel-scaffold chemical starting point for future PRODH-targeted therapies and metabolic interventions in lung cancer.

PMID:
42635425
Bibliographic data and abstract were imported from PubMed on 24 Aug 2026.

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