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5mg |
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10mg |
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50mg |
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100mg |
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ln Vitro |
Reporter gene detection demonstrated that silybin and isosilybin, the components of milk thistle, are responsible for suppressing PXR-mediated activation of CYP3A4 in milk thistle. Compared with silibinin, its isomer isosilybin is a greater inhibitor of PXR-mediated activation of CYP3A4. Isosilybin solutions at 89, 133 and 200 μM significantly reduced CYP3A4 induction by 64%, 82% and 88%, respectively. Isosilybin inhibits CYP3A4 induction with an IC50 of 74 μM[1]. Isosilybin B and isosilybin A are two diastereomers obtained from silymarin that possess anti-prostate cancer (PCA) action mediated through cell cycle arrest and activation of apoptosis. Treatment with isosilybin B and isosilybin A leads in growth inhibition and cell death of human prostate cancer LNCaP and 22Rv1 cells, as well as significant G(1) arrest and apoptosis [2]. Isosilybin B causes enhanced phosphorylation of Akt (Ser-473 and Thr-308) and Mdm2 (Ser-166), which is congruent with the restoration of androgen receptor levels by pretreatment with a PI3K inhibitor (LY294002). related to body degeneration. Isosilybin B therapy can accelerate the formation of complexes between Akt, Mdm2 and AR, hence boosting phosphorylation-dependent AR ubiquitination and subsequent destruction by the proteasome [3]. Isosilybin A strongly activated PPARγ at a dose of 30 μM (2.08±0.48-fold, p<0.01). Isosilybin A stimulates transactivation of the PPARγ-dependent luciferase reporter gene in a concentration-dependent manner. Computer docking studies have demonstrated that the binding manner of 3 is distinct from that of the inactive silymarin component, and there is an extra hydrogen bond with Ser342 in the entry area of the receptor ligand binding domain [4].
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References |
[1]. Mooiman KD, et al. Milk thistle's active components silybin and isosilybin: novel inhibitors of PXR-mediated CYP3A4 induction. Drug Metab Dispos. 2013 Aug;41(8):1494-504.
[2]. Deep G, et al. Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. Carcinogenesis. 2007 Jul;28(7):1533-42. [3]. Deep G, et al. Isosilybin B causes androgen receptor degradation in human prostate carcinoma cells via PI3K-Akt-Mdm2-mediated pathway. Oncogene. 2008 Jun 26;27(28):3986-98. [4]. Pferschy-Wenzig EM, et al. Identification of isosilybin a from milk thistle seeds as an agonist of peroxisome proliferator-activated receptor gamma. J Nat Prod. 2014 Apr 25;77(4):842-7 |
Molecular Formula |
C25H22O10
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Molecular Weight |
482.4362
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CAS # |
72581-71-6
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Related CAS # |
Silybin A;22888-70-6;Silybin;802918-57-6;Silybin B;142797-34-0
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O1C2C([H])=C(C([H])=C([H])C=2OC([H])(C2C([H])=C([H])C(=C(C=2[H])OC([H])([H])[H])O[H])C1([H])C([H])([H])O[H])C1([H])C([H])(C(C2=C(C([H])=C(C([H])=C2O1)O[H])O[H])=O)O[H]
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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 (~207.28 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 (5.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 (5.18 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 | 2.0728 mL | 10.3640 mL | 20.7280 mL | |
5 mM | 0.4146 mL | 2.0728 mL | 4.1456 mL | |
10 mM | 0.2073 mL | 1.0364 mL | 2.0728 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.