| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
5-HT Receptor 460 nM (IC50)
Syk Inhibitor II dihydrochloride targets spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase involved in immune cell signaling. Syk is activated upon phosphorylation and binds to ITAMs of FcRγ chains, mediating downstream signaling pathways related to platelet function and inflammation. The compound is a selective, reversible, ATP-competitive inhibitor of Syk with an IC50 of 41 nM. It shows high selectivity for Syk over other kinases. |
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| ln Vitro |
Syk Inhibitor II (compound 9a) dihydrochloride has a mild effect on PKCε, PKCβ2, ZAP-70, Btk and Itk, with IC50 values of 5.1 µM, 11 µM, 11.2 µM, 15.5 µM and 22.6 µM correspondingly [1].
Syk Inhibitor II dihydrochloride demonstrates potent in vitro activity against Syk with an IC50 of 41 nM. It inhibits 5-HT release from RBL cells with an IC50 of 460 nM, demonstrating its cellular activity. The compound selectively and reversibly blocks Syk in an ATP-competitive manner. Its cell-permeable nature allows it to effectively inhibit Syk-dependent signaling in various cell types, including mast cells and platelets. |
| ln Vivo |
Syk Inhibitor II (Compound 9a; 10-100 mg/kg) dihydrochloride, when subcutaneously injected 30 minutes before to antigen challenge, reduces allergic reactions in a dose-dependent manner with an ID50 of 13.2 mg/kg[1].
Syk Inhibitor II dihydrochloride shows in vivo activity by inhibiting Syk-mediated signaling pathways. As an ATP-competitive Syk inhibitor, it blocks downstream signaling related to platelet function and inflammation. The compound has been studied in models of immune-mediated inflammatory conditions where Syk plays a critical role. Its ability to inhibit 5-HT release from RBL cells suggests potential efficacy in mast cell-related inflammatory responses. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for Syk Inhibitor II dihydrochloride involves assessing its ATP-competitive inhibition of Syk kinase activity. Recombinant Syk kinase is incubated with the compound, ATP, and a substrate peptide. Kinase activity is measured by detecting phosphorylated substrate using techniques such as radiometric assays or fluorescence-based assays. The IC50 value of 41 nM is determined from dose-response curves. Selectivity profiling against other kinases confirms its specificity for Syk.
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| Cell Assay |
The in vitro cell-based assay for Syk Inhibitor II dihydrochloride involves treating RBL (rat basophilic leukemia) cells with the compound and measuring 5-HT (serotonin) release. RBL cells are stimulated through FcεRI receptors to induce Syk-dependent signaling and 5-HT release. The compound inhibits 5-HT release with an IC50 of 460 nM. Additional assays may measure Syk phosphorylation and downstream signaling by Western blotting or ELISA in various cell types, including platelets and immune cells.
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| Animal Protocol |
Animal/Disease Models: ICR mice[1]
Doses: 10, 30, 100 mg/kg Route of Administration: Sc; 30 min before antigen challenge Experimental Results: Inhibited the anaphylaxis reaction dose-dependently with an ID50 value of 13.2 mg/kg. In vivo animal experiments for Syk Inhibitor II dihydrochloride are conducted in models of inflammation and platelet function where Syk plays a critical role. Animals are administered the compound via appropriate routes, and pharmacological responses such as inhibition of platelet aggregation, reduction of inflammatory mediators, or attenuation of disease severity are measured. The compound’s ability to block Syk-mediated signaling in vivo is assessed through pharmacodynamic markers. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of Syk Inhibitor II dihydrochloride are not extensively reported. The compound has a molecular formula of C14H15F3N6O•2HCl and a purity of ≥98%. It is soluble in DMF (2 mg/mL), DMSO (30 mg/mL), ethanol (0.3 mg/mL), and PBS pH 7.2 (10 mg/mL). The compound is typically stored at -20°C. Further pharmacokinetic studies are required to determine its half-life, bioavailability, and clearance.
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| Toxicity/Toxicokinetics |
Toxicological data for Syk Inhibitor II dihydrochloride are not extensively documented. As a research compound, its safety profile is evaluated in standard cytotoxicity and acute toxicity assays. The compound is classified for research use only and is not intended for human therapeutic use. Comprehensive toxicological characterization would be required prior to any clinical development.
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| References | |
| Additional Infomation |
Syk Inhibitor II dihydrochloride (CAS 227449-73-2) is a cell-permeable, pyrimidine-carboxamide compound that selectively and reversibly blocks Syk (IC50=41 nM) in an ATP-competitive manner. It has a molecular formula of C14H15F3N6O•2HCl and a purity of ≥98%. The compound inhibits 5-HT release from RBL cells with an IC50 of 460 nM. It is used in research on platelet function, inflammation, and immune signaling. It is not approved for clinical use.
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| Molecular Formula |
C14H17CL2F3N6O
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|---|---|
| Molecular Weight |
413.23
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| Exact Mass |
448.1
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| CAS # |
227449-73-2
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| Related CAS # |
Syk Inhibitor II;726695-51-8;Syk Inhibitor II dihydrochloride dihydrate;1965323-05-0
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| PubChem CID |
90664659
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.612
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
422
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.FC(C1C=CC=C(C=1)NC1C(C(N)=O)=CN=C(N=1)NCCN)(F)F
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| InChi Key |
OWOVYLSSMDVDIW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H15F3N6O.2ClH/c15-14(16,17)8-2-1-3-9(6-8)22-12-10(11(19)24)7-21-13(23-12)20-5-4-18;;/h1-3,6-7H,4-5,18H2,(H2,19,24)(H2,20,21,22,23);2*1H
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| Chemical Name |
2-(2-aminoethylamino)-4-[3-(trifluoromethyl)anilino]pyrimidine-5-carboxamide;dihydrochloride
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4200 mL | 12.0998 mL | 24.1996 mL | |
| 5 mM | 0.4840 mL | 2.4200 mL | 4.8399 mL | |
| 10 mM | 0.2420 mL | 1.2100 mL | 2.4200 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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