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Table 2 Enzymes in glycolysis for possible PDAC therapy

From: Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: causes, characteristics and clinical applications

Enzymes Compounds or methods Introductions Ref
HK 2-DG Inhibitor of HK, acts as a glucose analog phosphorylated by HK that then blocks glycolysis [117]
3-BP Inhibitor of HK, suppresses activity of HK and glycolysis [118]
Novel MJ analog Inhibitor of HK, disrupts VDAC and HK-2 interactions on the mitochondrial membrane and then inhibits glycolysis [119]
Downregulate HOTAIR Inhibits the expression of HK in both the serum and tumor tissue to suppress glycolysis and tumor growth [120]
PFK 3-PO Inhibits PFKFB3, reduces the synthesis of F-2,6-BP and then inhibits PFK activity [125]
Activates AMPK Attenuates phosphofructo-2-kinase activity and increases fructose-2-biphosphatase activity to inhibit PFK [123]
Target miR-135 Inhibits PFK, can construct a glutamine-deficient condition in combination with a glutaminase inhibitor [127]
PK Downregulate PKM-2 Resumes p38 mitogen–activated protein kinase activity and enhances gemcitabine-resistant cell apoptosis [130]
TEPP-46 Activates the tetramer of PKM-2 and impairs tumor growth and proliferation [129]
TEPP-46 and FX-11 Significant antitumor effect and limited toxicity in finished phase III trial [129]
LDH FX-11 Inhibitor of LDH-A, suppresses glycolysis and tumor growth [133]
Target FOXM1 FOXM1/LDH-A pathway promotes glycolysis and lactate production [39]
Novel NHI inhibitors Targets LDH-A, inhibits glycolysis, growth, and invasion in PDAC [135]
TEPP-46 and FX-11 Significant antitumor effect and limited toxicity in finished phase III trial [129]
Aldolase TX-2098 Suppresses HIF-1α, GLUT1, and Aldolase A, leads to distinct antitumor effect on PDAC xenograft model [139]
NDB Inhibitor of Aldolase A, has high affinity and resistance to hydrolysis, suppresses glycolysis and tumor growth [140]
GAPDH KA Inhibitor of GAPDH, leads to low glycolytic flux in cancer cells and little cytotoxic to normal tissue [142]
Iodoacetate Inhibitor of GAPDH, leads to reduced glycolysis and cell survival [143]
PGK Target SMAD4 Inhibits expression and subcellular localization of PGK-1 to decrease EMT and glycolysis in PDAC [150]
Activate PTEN Dephosphorylates PGK-1 at Y324 to block glycolysis and proliferation in cancer cells [151]
PGAM KH3 Allosteric suppressor of PGAM-1, represses glycolysis and cell proliferation with limited cytotoxicity [152]
Target PTMs Targets PTMs such as PGAM-1 dephosphorylation and deacetylation to attenuate enzymatic activity [154] [155] [156]
Enolase Sodium fluoride Inhibitor of enolase, decreases glycolysis and invasion in PDAC [212]
SF2312 Specific inhibitor of enolase, reduces glycolysis and invasion [161]
PGI 6-phosphogluconic acid Possible inhibitor of PGI, induces low PGI activity and attenuates glycolysis [212]
Others
KRAS AMG-510 First inhibitor of KRAS, causes a decline in KRASG12C tumor growth [213]
BRCA1/2 Olaparib Approved by the FDA for BRCA1/2-mutant metastatic PDAC [214]