Abstract 4682: Elucidating the mechanisms of 2-deoxy-D-glucose (2-DG) and 2-deoxy-D-glucose phoaphate (2-DG-P) in maintaining gastrointestinal homeostasis

Abstract 2-Deoxy-D-glucose (2-DG), a polypharmacological agent, has shown promise in treating various pathological conditions, including cancer, bacterial and viral infections, and as an adjuvant to radio-chemo-therapy. 2-DG exerts its effects by inhibiting glycolysis, disrupting protein N-glycosylation, inducing endoplasmic reticulum stress, autophagy, and apoptosis. Our recent studies demonstrated that 2-DG mitigates bacterial infection-induced inflammation and colitis, and proposed its potential as a radiation countermeasure agent. Utilizing a colonoid model, we investigated the mechanisms underlying 2-DG's maintenance of gastrointestinal homeostasis. Specifically, we explored its interaction with Doublecortin-like kinase 1 (DCLK1), a protein with two major isoforms, DCLK1-L and DCLK1-S.Here, 2-DG-Phosphate (2-DG-P), the non-metabolizable product of 2-DG, is also implicated in this process. Combining in silico molecular docking of 2-DG and 2-DG-P with DCLK1, we propose that 2-DG-P, along with 2-DG, may serve as potential candidates for radioprotection and mitigation of irradiation-induced gastrointestinal acute radiation syndrome (GI-ARS). Citation Format: Rao V. Papineni, Shahid Umar, Prashanthi Karyala, Kavya Ramesh, Badal Roy. Elucidating the mechanisms of 2-deoxy-D-glucose (2-DG) and 2-deoxy-D-glucose phoaphate (2-DG-P) in maintaining gastrointestinal homeostasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4682.