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

Year: 2026
Type: article
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.
DOI: 10.1080/14756366.2026.2719719
Authors: Yuxuan Zhou, Dingyuan Bai, Zhihan Li, Ciqin Li, Chunqiong Li, Mengyao Chen, Cheng Guo, Jun Yan, Yonglong Han, Quanjun Yang
Institutions: Shanghai Jiao Tong University, Shanghai Sixth People's Hospital, Shanghai Ocean University, Beijing University of Chinese Medicine, Donghua University, Peking University
Language: English
Subfield: Biochemistry
Open Access status: gold
Estimated APC paid: $2,306
OpenAlex ID: W7204111397
FWCI:
Cites: 32
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