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NHI-Glc-2
- Development stage
- Preclinical
- Lead developer
- Vrije University Medical Center
- Modality
- Small Molecules
- Administration
- Intravenous, Intratumoral
01
Overview
NHI-Glc-2 is a glucose-conjugated small molecule inhibitor of lactate dehydrogenase A (LDH-A), specifically designed to target hypoxic cancer cells in pancreatic ductal adenocarcinoma (PDAC). By conjugating an N-hydroxyindole-based LDH-A inhibitor with glucose, the compound leverages the overexpression of glucose transporter 1 (GLUT-1) in tumor cells to enhance cellular uptake. LDH-A is a key enzyme in aerobic glycolysis (the Warburg effect), and its inhibition disrupts the metabolic adaptation of tumor cells to hypoxic environments. Preclinical studies have demonstrated that NHI-Glc-2 inhibits PDAC cell growth in the micromolar range under hypoxia, disrupts 3D spheroid integrity, and shows synergistic effects when combined with gemcitabine. In orthotopic PDAC models, it has shown significant tumor growth inhibition and favorable pharmacokinetics.
- Other names
- glucose conjugated lactate dehydrogenase inhibitor NHI-Glc-2
02
Targets
LDH (L-lactate dehydrogenase A chain)GLUT1 (Glucose transporter 1)
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