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1-(((cyclohexyloxy)carbonyl)oxy)ethyl 6-aminonicotinate
- Development stage
- Preclinical
- Lead developer
- The University of Tokyo
- Modality
- Small Molecules
01
Overview
1-(((cyclohexyloxy)carbonyl)oxy)ethyl 6-aminonicotinate, also known as compound 5i, is a small molecule prodrug of 6-aminonicotinic acid (6ANA). It was developed as a more potent and less toxic alternative to 6-aminonicotinamide (6AN) for targeting the epigenetic reprogramming in metastatic pancreatic ductal adenocarcinoma (PDAC). The compound is metabolized via the Preiss-Handler pathway into 6-amino-NADP+, which serves as a potent inhibitor of 6-phosphogluconate dehydrogenase (6PGD). Inhibition of 6PGD leads to the reversal of histone 3 lysine 9 trimethylation (H3K9me3) loss, a characteristic of distant metastatic PDAC cells. Preclinical studies have demonstrated that 5i has significant antiproliferative activity and reduced neurotoxicity compared to its predecessor, 6AN.
- Other names
- 1-(((cyclohexyloxy)carbonyl)oxy)ethyl 6-aminonicotinate
02
Targets
PGD (6-Phosphogluconate dehydrogenase)
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