Table 2.

Enzymes in glycolysis for possible PDAC therapy

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]