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| Glabrescione B (GlaB) was extracted and purified from seeds of Derris glabrescens (Leguminosae) Glabrescione B — Glabrescione B (GlaB) is a naturally occurring isoflavone-derived small molecule originally isolated from the seeds of Derris glabrescens. It is classified as a direct GLI transcription-factor inhibitor and experimental Hedgehog-pathway antagonist. Unlike clinically used Smoothened inhibitors, GlaB acts downstream of SMO by binding the zinc-finger DNA-binding region of GLI1 and disrupting GLI1-DNA interaction. This downstream mechanism is potentially relevant to tumors with canonical or non-canonical GLI1 activation and to resistance mechanisms that bypass SMO. GlaB remains an experimental preclinical compound rather than an approved anticancer drug. Primary mechanisms (ranked):
Bioavailability / PK relevance: Free GlaB has poor aqueous solubility and unfavorable formulation characteristics that substantially limit systemic translation. Nanocarrier approaches, including polymeric nanocapsules, self-assembling mPEG-cholane micelles, and liposomes, have been developed to improve solubility, circulation exposure, tumor delivery, and pharmacokinetics. In mouse models, micellar GlaB achieved longer systemic exposure and delivery across the blood-brain barrier; newer liposomal formulations produced higher exposure and slower elimination than free GlaB. In-vitro vs systemic exposure relevance: Many mechanistic experiments use approximately 1–10 µM GlaB for 24–72 hours. These concentrations should not be assumed to be achievable or maintainable with unformulated systemic GlaB. The major translational issue is therefore drug delivery rather than evidence that oral or conventional systemic dosing can reproduce standard in-vitro concentrations. Nanocarrier formulation materially changes this exposure constraint. Clinical evidence status: Preclinical only. Antitumor activity has been demonstrated in cultured cells, cancer stem-cell assays, xenografts, orthotopic medulloblastoma models, patient-derived renal cancer organoids, and other animal models. No human therapeutic trial of Glabrescione B and no FDA, EMA, or Health Canada approval were identified as of August 2026. Current development remains focused on formulation, pharmacokinetics, and preclinical validation. Glabrescione B Cancer-Relevant Mechanisms
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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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| 7297- | GlaB, | H-NMR metabolomics reveals the Glabrescione B exacerbation of glycolytic metabolism beside the cell growth inhibitory effect in glioma |
| - | vitro+vivo, | GBM, | NA |
| 7298- | GlaB, | Glycolytic Metabolic Remodeling by the Truncate of Glioma-Associated Oncogene Homolog 1 in Triple-Negative Breast Cancer Cells |
| - | in-vitro, | BC, | 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#:90 Target#:947 State#:% Dir#:%
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