Table 2 Enzymes in glycolysis for possible PDAC therapy

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]

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]

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]

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]

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]

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]

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]

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]

Sodium fluoride

Inhibitor of enolase, decreases glycolysis and invasion in PDAC

[212]

SF2312

Specific inhibitor of enolase, reduces glycolysis and invasion

[161]

6-phosphogluconic acid

Possible inhibitor of PGI, induces low PGI activity and attenuates glycolysis

[212]

AMG-510

First inhibitor of KRAS, causes a decline in KRASG12C tumor growth

[213]

Olaparib

Approved by the FDA for BRCA1/2-mutant metastatic PDAC

[214]