The Warburg effect is a metabolic phenomenon in which cancer cells preferentially use glycolysis for energy production, even in the presence of oxygen. Targeting the pathways involved in the Warburg effect is a promising strategy for cancer treatment.
The Warburg effect is always accompanied by a hypoxic condition, and activation of HIF-1a contributes to the Warburg effect through coordinated upregulation of glycolysis and downregulation of oxidative phosphorylation.
Warburg effect (GLUT1, LDHA, HK2, and PKM2).
Here are some of the key pathways and potential targets:
Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓
1.Glycolysis Inhibitors:(2-DG, 3-BP)
-HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis
-PFK1 Inhibitors: such as PFK-158, can reduce glycolysis
-PFKFB Inhibitors:
-PKM2 Inhibitors: (Shikonin)
-Can reduce glycolysis
-LDH Inhibitors: (Gossypol, FX11)
-Reducing the conversion of pyruvate to lactate.
-Inhibiting the production of ATP and NADH.
-GLUT1 Inhibitors: (phloretin, WZB117)
-A key transporter involved in glucose uptake.
-GLUT3 Inhibitors:
-PDK1 Inhibitors: (dichloroacetate)
- A key enzyme involved in the regulation of glycolysis.
2.Gluconeogenesis pathway:
-FBP1 Activators: can increase gluconeogenesis
-PEPCK1 Inhibitors: can reduce gluconeogenesis
3.Pentose phosphate pathway:
-G6PD Inhibitors: can reduce the pentose phosphate pathway
4.Mitochondrial metabolism:
-MPC1 Inhibitors: can reduce mitochondrial metabolism and inhibit cancer
-SDH Inhibitors: can reduce mitochondrial metabolism and inhibit cancer cell growth.
5.Hypoxia-inducible factor 1 alpha (HIF1α) pathway:
-HIF1α inhibitors: (PX-478,Shikonin)
-Reduce expression of glycolytic genes and inhibit cancer cell growth.
6.AMP-activated protein kinase (AMPK) pathway:
-AMPK activators: (metformin,AICAR,berberine)
-Can increase AMPK activity and inhibit cancer cell growth.
7.mTOR pathway:
-mTOR inhibitors:(rapamycin,everolimus)
-Can reduce mTOR activity and inhibit cancer cell growth.
Home