CBR-470-1 is a potent inhibitor of glycolytic phosphoglycerate kinase 1 (PGK1) that activates NRF2 by increasing methylglyoxal levels. CBR-470-1 is a non-covalent Nrf2 activator with neuroprotective activity that protects SH-SY5Y neuronal cells from MPP+-induced cytotoxicity by activating the Keap1-Nrf2 cascade. cytotoxicity induced by MPP+.

Acriflavine Hydrochloride (Acriflavine HCl) is a HIF-1α inhibitor. It acts by targeting HIF-1α-mediated pathways and decreasing the level of PGK1, VEGF, and HIF-1α in vitro and in vivo.

Z57346765 is a specific PGK1(Phosphoglycerate kinase 1) inhibitor that inhibits PGK1-dependent cell proliferation by decreasing the metabolic enzyme activity of PGK1 during glycolysis. In the clinical phase, Z57346765 had a dose-dependent inhibitory effect on locally advanced renal clear cell carcinoma (KIRC) by inducing changes in the expression of genes related to cell metabolism, DNA replication, and the cell cycle.

PGK1-IN-1 (Compound 6e) is a potent and selective inhibitor of PGK1 with an IC50 of 33 nM, effectively hindering PGK1-mediated glycolytic metabolism and reducing glucose consumption and lactate production. Additionally, PGK1-IN-1 promotes the accumulation of Nrf2 and the expression of HO-1, while suppressing the transcription and protein levels of inflammatory cytokines IL-1β and IL-6. It shows potential in ameliorating experimental colitis in mice induced by dextran sulfate sodium (DSS) and can be utilized in research on inflammatory bowel disease (IBD).

DC-PGKI is an orally active ATP-competitive inhibitor of PGK1, with an IC50 of 0.16 μM and a Kd of 99.08 nM. It stabilizes PGK1 both in vitro and in vivo, inhibiting glycolytic activity and PGK1's kinase function. This inhibition induces the accumulation of NRF2 (nuclear factor erythroid 2-related factor 2, NFE2L2), which then translocates to the nucleus, binds to the proximal regions of IL-1β and IL-6 genes, and inhibits their LPS-induced expression. DC-PGKI is applicable for research in colitis.