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Purity: ≥98%
R112 is a novel, potent and ATP-competitive inhibitor of Syk kinase with a Ki of 96 nM. R112 prevented degranulation brought on by allergen (dust mite) in basophils (histamine release, EC(50) = 490 nmol/L), anti-IgE cross-linking in mast cells (tryptase release, effective concentration for 50% inhibition [EC(50)] = 353 nmol/L), or both. R112 also inhibited the production of leukotriene C4 and every proinflammatory cytokine that was examined. R112 was found to be an ATP-competitive spleen tyrosine kinase (Syk) inhibitor by subsequent molecular characterization (inhibitory constant [K(i)] = 96 nmol/L). It had a rapid onset of action and reversible inhibition. Mast cells incubated with R112 demonstrated that prolonged activation of the FcvarepsilonRI-Lyn-spleen tyrosine kinase pathway was necessary for mast cell cytokine production. R112 was able to totally inhibit the three IgE-induced mast cell functions of degranulation, lipid mediator production, and cytokine production, in contrast to other mast cell inhibitors. IgE receptor cross-linking-induced mast cell activation cascades were all potently, totally, and quickly abrogated by R112. R112 and its derivatives present a novel approach to the management of allergic rhinorrhea.
| Targets |
Syk (Ki = 96 nM); c-Met (IC50 = 32 nM)
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|---|---|
| ln Vitro |
R112 (0.001-10 μM; 1 h) prevents the release of histamine and anti-IgE-mediated tryptase with EC50s of 0.353 and 0.28 μM, the release of histamine when basophils are stimulated with an EC50 value of 0.49 μM, and the release of LTC4, TNF-α, GM-CSF, and IL-8 with EC50s of 0.115, 2.01, 1.58, and 1.75 μM, respectively[1].
R112 (0-10 μM; 40 min) reduces the phosphorylation of the Syk target LAT (Y191)[1]. |
| Cell Assay |
Cell Line: Human mast cells
Concentration: 0.4, 2 and 10 μM Incubation Time: 40 min Result: Inhibited phosphorylation of the Syk target LAT (Y191) and also inhibited phosphorylation of Syk downstream events. |
| References |
| Molecular Formula |
C16H13FN4O2
|
|---|---|
| Molecular Weight |
312.2984
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| Exact Mass |
312.102
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| Elemental Analysis |
C, 61.53; H, 4.20; F, 6.08; N, 17.94; O, 10.25
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| CAS # |
575474-82-7
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| Related CAS # |
575474-82-7
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| PubChem CID |
9904854
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| Appearance |
White to off white solid powder
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| LogP |
3.009
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| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
376
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1=C([H])N=C(N=C1N([H])C1C([H])=C([H])C([H])=C(C=1[H])O[H])N([H])C1C([H])=C([H])C([H])=C(C=1[H])O[H]
|
| InChi Key |
TVKGTSHBQZEFEE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H13FN4O2/c17-14-9-18-16(20-11-4-2-6-13(23)8-11)21-15(14)19-10-3-1-5-12(22)7-10/h1-9,22-23H,(H2,18,19,20,21)
|
| Chemical Name |
3-[[5-fluoro-2-(3-hydroxyanilino)pyrimidin-4-yl]amino]phenol
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| Synonyms |
R 112; R112; R112
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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: 55~62 mg/mL (176.1~198.5 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (8.81 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 27.5 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: ≥ 2.75 mg/mL (8.81 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 27.5 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: ≥ 2.75 mg/mL (8.81 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 | 3.2020 mL | 16.0102 mL | 32.0205 mL | |
| 5 mM | 0.6404 mL | 3.2020 mL | 6.4041 mL | |
| 10 mM | 0.3202 mL | 1.6010 mL | 3.2020 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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