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Purity: ≥98%
Benvitimod (Tapinarof; WB1001; GSK2894512) is a naturally occurring aryl hydrocarbon receptor (AhR) agonist (EC50 = 13 nM) approved in China for treating plaque psoriasis. It also acts as a non-steroidal anti-inflammatory drug (NSAID) and an immunomodulator. It has the potential for the treatment of atopic dermatitis and other autoimmune diseases. Benvitimod demonstrated efficacy in patients with psoriasis and atopic dermatitis, although the biologic target and mechanism of action had been unknown. Tapinarof has been proposed to be an aryl hydrocarbon receptor (AhR) agonist with an EC50 of 13 nM. The anti-inflammatory properties of tapinarof are mediated through activation of the aryl hydrocarbon receptor (AhR). We show that tapinarof binds and activates AhR in multiple cell types, including cells of the target tissue-human skin. In addition, tapinarof moderates proinflammatory cytokine expression in stimulated peripheral blood CD4+ T cells and ex vivo human skin, and impacts barrier gene expression in primary human keratinocytes; both of these processes are likely to be downstream of AhR activation based on current evidence. That the anti-inflammatory properties of tapinarof derive from AhR agonism is conclusively demonstrated using the mouse model of imiquimod-induced psoriasiform skin lesions. Topical treatment of AhR-sufficient mice with tapinarof leads to compound-driven reductions in erythema, epidermal thickening, and tissue cytokine levels. In contrast, tapinarof has no impact on imiquimod-induced skin inflammation in AhR-deficient mice. In summary, these studies identify tapinarof as an AhR agonist and confirm that its efficacy is dependent on AhR.
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| ln Vitro |
Tapinarof directly binds to the AhR pathway to initiate it. AhR nuclear translocation is dose-dependently induced by tapinarof in immortalized keratinocytes (HaCaT) (EC50=0.16 nM)[1].
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| ln Vivo |
In mice treated with IMQ, tapinarof reduces inflammation by acting through AhR. In C57Bl/6 background, AhR-sufficient mice show a lower clinical score following treatment with 6-formylindolo(3,2-b)carbazole (FICZ) or Tapinarof. Conversely, Tapinarof's anti-inflammatory actions had little effect on AhR KO mice. These experiments use FICZ as a comparator, and the results are similar: wild-type mice, but not AhR KO mice, have significantly lower inflammatory responses[1].
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| Enzyme Assay |
Kinetic binding experiments (fluorescence-based assay)[1]
Intrinsic fluorescence signals of 100 nM compound were monitored using the BioTek Synergy 4 microplate reader (310 nm excitation/400 nm emission) in black 96-well plates. Increasing concentrations of human or mouse AHR-ARNT protein complexes were mixed with 100 nM compound in 20 mM Tris (pH 8.0), 400 mM NaCl buffer. Fluorescence was measured and Kd values were calculated by fitting the curves in GraphPad Prism 6. |
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| Cell Assay |
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| Animal Protocol |
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| References |
[1]. Smith SH, et al. Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans. J Invest Dermatol. 2017 Oct;137(10):2110-2119
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| Molecular Formula |
C17H18O2
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|---|---|
| Molecular Weight |
254.32362
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| Exact Mass |
254.13067
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| Elemental Analysis |
C, 80.28; H, 7.13; O, 12.58
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| CAS # |
79338-84-4
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| Appearance |
White to light yellow solid powder
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| LogP |
4.6
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| tPSA |
40.5A^2
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| SMILES |
OC1=C(C(C)C)C(O)=CC(/C=C/C2=CC=CC=C2)=C1
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| InChi Key |
ZISJNXNHJRQYJO-CMDGGOBGSA-N
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| InChi Code |
InChI=1S/C17H18O2/c1-12(2)17-15(18)10-14(11-16(17)19)9-8-13-6-4-3-5-7-13/h3-12,18-19H,1-2H3/b9-8+
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| Chemical Name |
3,5-Dihydroxy-4-isopropylstilbene
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| Synonyms |
GSK-2894512; WB-1001; tapinarof; WBI-1001; WB1001; WBI 1001; GSK 2894512; GSK2894512; 3,5-DH4IS;
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~393.21 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.83 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 (9.83 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 (9.83 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 | 3.9321 mL | 19.6603 mL | 39.3205 mL | |
| 5 mM | 0.7864 mL | 3.9321 mL | 7.8641 mL | |
| 10 mM | 0.3932 mL | 1.9660 mL | 3.9321 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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