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| The (R)-enantiomer of alkannin is known as shikonin, and the racemic mixture of the two is known as shikalkin. Shikonin is a naphthoquinone derivative primarily isolated from the roots of plants in the Boraginaceae family (e.g., Lithospermum erythrorhizon). Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao' -Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with anti-inflammatory properties -Quinone methides (QMs) are highly reactive intermediates formed from natural compounds like shikonin -ic50 cancer cells 1-10uM, normal cells >10uM -known as Glycolysis inhibitor: ( inhibit pyruvate kinase M2 (PKM2*******), a key enzyme in the glycolytic pathway) Available from mcsformulas.com Shikonin Pro Liposomal, 30 mg Also In Glycolysis Inhibithree(100 mg PHLORIZIN,10 mg TANSHINONE IIA, 8 mg Shikonin) -Note half-life15-30mins or 8hr?. BioAv low, poor water solubility Pathways: - usually induce ROS production in cancer cells, and reduce ROS in normal cells. - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ GPx4↓ - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, ERK↓ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK, P53↑, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells
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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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| 2356- | SK, | ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment |
| - | in-vitro, | Ovarian, | CaOV3 | - | in-vitro, | Ovarian, | OV90 | - | in-vivo, | NA, | NA |
| 2417- | SK, | Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer |
| - | in-vitro, | Lung, | A549 | - | in-vitro, | Lung, | H446 |
| 2185- | SK, | Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic Glycolysis |
| - | in-vitro, | Lung, | LLC1 | - | in-vitro, | Melanoma, | B16-BL6 | - | in-vivo, | NA, | NA |
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#:150 Target#:947 State#:% Dir#:%
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