| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Gli1-DNA Interaction[1]
Gli1 (a downstream effector of the Hedgehog (Hh) signaling pathway). By binding to Gli1, Glabrescione B prevents its interaction with DNA, thus suppressing Gli1-mediated transcription. |
|---|---|
| ln Vitro |
Glabrescione B (5 μM; 24-72 hours) suppresses the proliferation of Gli-dependent basal cell carcinoma[2]. Glabrescione B (1-10 μM; 24-48 hours) reduces Gli1 mRNA expression levels[2].
Glabrescione B (1-10 uM; 24-48 h) decreases Gli1 mRNA expression levels in ASZ001 basal cell carcinoma (BCC) cells. At 5 uM (24-72 h), it inhibits the growth of Gli-dependent BCC cells and suppresses the self-renewal and clonogenic abilities of tumor-derived stem cells. |
| ln Vivo |
In female NOD/SCID mice bearing ASZ001 BCC allografts, Glabrescione B (100 micromol/kg; i.p.; every other day for 18 days) resulted in a significant reduction of tumor growth and also lowered Gli1 mRNA expression levels in the tumor tissue.
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| Enzyme Assay |
Cell-free Gli1-DNA interaction assays are performed by incubating recombinant Gli1 protein with a biotinylated DNA probe containing the Gli1 binding consensus sequence. Glabrescione B is added at increasing concentrations (0.01-100 uM) to the reaction mix. The amount of Gli1 bound to the DNA is quantified by a streptavidin-based ELISA or AlphaScreen assay after a 30-60 min incubation at room temperature.
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| Cell Assay |
Cell Proliferation Assay [1]
Cell Types: ASZ001 BCC cells Tested Concentrations: 5 μM Incubation Duration: 24-72 hrs (hours) Experimental Results: Basal cell carcinoma cell proliferation was impaired. Western Blot Analysis[1] Cell Types: ASZ001 BCC cells Tested Concentrations: 1-10 μM Incubation Duration: 24-48 hrs (hours) Experimental Results: Gli1 mRNA expression levels was decreased. ASZ001 murine basal cell carcinoma cells are cultured in 96-well plates and treated with Glabrescione B at various concentrations (1-10 uM) for 24-72 hours. Cell proliferation is assessed by MTT or BrdU incorporation assay. For Gli1 mRNA expression analysis, cells are treated with Glabrescione B (1-10 uM; 24-48 h), then total RNA is extracted and Gli1 mRNA levels are quantified by qRT-PCR normalized to GAPDH. |
| Animal Protocol |
Animal/Disease Models: Female NOD/SCID (severe combined immunodeficient) mouse (ASZ001 BCC allografts)[2]
Doses: 100 μmol/kg Route of Administration: Ip; every second day for 18 days Experimental Results: A significant reduction of tumor growth as well as Gli1 mRNA levels was observed. Female NOD/SCID mice are subcutaneously inoculated with ASZ001 BCC cells. Once tumors reach an appropriate size, Glabrescione B (100 micromol/kg) is administered via intraperitoneal injection every other day for 18 days. Tumor volumes are measured with calipers every 2-3 days. At the end of the study, tumors are excised for Gli1 mRNA quantification by qRT-PCR. Plasma and tumor drug concentrations can be analyzed by LC-MS/MS. |
| ADME/Pharmacokinetics |
Glabrescione B has a molecular weight of 450.53 (C27H30O6) and is soluble in DMSO. It is typically administered by intraperitoneal injection in vivo. Pharmacokinetic parameters such as oral bioavailability, plasma half-life (t1/2), and tissue distribution have not been characterized in detail. The compound can be formulated using 5% DMSO + 30% PEG300 + 5% Tween 80 + 60% ddH2O for injection.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for Glabrescione B in the literature. As a natural product-based Gli1 inhibitor, its safety profile is not fully characterized. In preclinical studies, at the reported dose of 100 micromol/kg, no overt signs of toxicity were observed; however, comprehensive toxicological assessments, including acute and repeat-dose toxicity studies, have not been published.
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| References | |
| Additional Infomation |
Glabrescione B is a methoxyisoflavone.
Other information: Glabrescione B is a research-grade natural isoflavone, not an FDA-approved drug. It is the first compound described to directly bind to Gli1 and interfere with its DNA-binding ability. It has been investigated as a potential therapeutic candidate for Hedgehog-driven cancers, including basal cell carcinoma and intrahepatic cholangiocarcinoma. Purity ≥98%, CAS# 65893-94-9. For research use only. |
| Molecular Formula |
C27H30O6
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|---|---|
| Molecular Weight |
450.52
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| Exact Mass |
450.204
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| CAS # |
65893-94-9
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| PubChem CID |
44257338
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| Appearance |
White to off-white solid powder
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| LogP |
6.167
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
33
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| Complexity |
746
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=CCOC1=C(C=C(C=C1)C2=COC3=C(C2=O)C(=CC(=C3)OC)OC)OCC=C(C)C)C
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| InChi Key |
RHXDATRKLOYVTC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H30O6/c1-17(2)9-11-31-22-8-7-19(13-23(22)32-12-10-18(3)4)21-16-33-25-15-20(29-5)14-24(30-6)26(25)27(21)28/h7-10,13-16H,11-12H2,1-6H3
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| Chemical Name |
3-[3,4-bis(3-methylbut-2-enoxy)phenyl]-5,7-dimethoxychromen-4-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (221.97 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.55 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.55 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2197 mL | 11.0983 mL | 22.1966 mL | |
| 5 mM | 0.4439 mL | 2.2197 mL | 4.4393 mL | |
| 10 mM | 0.2220 mL | 1.1098 mL | 2.2197 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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