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| Methylene blue (MB), also known as methylthioninium chloride, is a thiazine dye that can be used as a medication, and can be administered orally, subcutaneously or intravenously. Mainly used to treat methemoglobinemia by chemically reducing the ferric iron in hemoglobin to ferrous iron Methylene blue is commonly used in medical practice, especially as a dye in microbiological staining Antidote in cyanide poisoning: an oxidation-reduction indicator: an antiseptic Pathways: - may increases the oxygen consumption of normal tissues having aerobic glycolysis, and of tumors - generate reactive oxygen species (ROS) upon light activation -effects on mitochondrial metabolism may contribute to modulation of apoptosis and energy metabolism in cancer cells. -can affect the generation of reactive oxygen species. -Historically, it was used in patients with urinary tract infection -MB has also been used as a tracer for cancer diagnosis and as a photosensitizer for cancer treatment -shifts redox balance and can promote OXPHOS over glycolysis in some models(reverse Warburg effect) -can cross BBB and reach brain at concentrations 10 times higher than that in the circulation -causes shift from shift from glycolysis to oxidative phosphorylation. -reduces glutathione reductase GSR (an enzyme of glutathione metabolism), context- and concentration-dependent
Time-Scale Flag (TSF): P / R / G
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| The Warburg effect (aerobic glycolysis) is a metabolic phenotype where many cancer cells use high glycolytic flux and lactate production even when oxygen is available. Tumors often contain hypoxic regions that further drive glycolysis, but Warburg metabolism can also occur under normoxic conditions (“pseudo-hypoxia”) via oncogenic signaling and metabolic rewiring. Hypoxia-inducible factor 1 alpha (HIF-1α) is one important driver in hypoxic tumor regions. HIF-1α upregulates glycolytic genes (e.g., GLUT1, HK2, LDHA) and promotes reduced mitochondrial pyruvate oxidation in part through induction of PDK (which inhibits PDH), shifting carbon toward lactate. Warburg effect (GLUT1, LDHA, HK2, and PKM2).Classic HIF-Warburg axis: PDK1 and MCT4 (SLC16A3) (pyruvate gate + lactate export). 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. PDK inhibitors (e.g., DCA) activate PDH and shift pyruvate into TCA/OXPHOS, reducing lactate pressure. 2.Pentose phosphate pathway: - G6PD Inhibitors: can reduce the pentose phosphate pathway 3.Hypoxia-inducible factor 1 alpha (HIF1α) pathway: - HIF1α inhibitors: (PX-478,Shikonin) -Reduce expression of glycolytic genes and inhibit cancer cell growth. 4.AMP-activated protein kinase (AMPK) pathway: -AMPK activators: (metformin,AICAR,berberine) -Can increase AMPK activity and inhibit cancer cell growth. 5.mTOR pathway: - mTOR inhibitors:(rapamycin,everolimus) -Can reduce mTOR activity and inhibit cancer cell growth. Warburg Targeting Matrix (Cancer Metabolism)
Time-Scale Flag (TSF): P / R / G
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| 2540- | M-Blu, | Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 2542- | M-Blu, | In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death |
| - | in-vitro, | Ovarian, | OV1369 | - | in-vitro, | Ovarian, | OV1946 | - | in-vitro, | Nor, | ARPE-19 |
| 2545- | M-Blu, | Reversing the Warburg Effect as a Treatment for Glioblastoma |
| - | in-vitro, | GBM, | U87MG | - | NA, | AD, | NA | - | in-vitro, | GBM, | A172 | - | in-vitro, | GBM, | T98G |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:12 Target#:947 State#:% Dir#:%
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