| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
IC50: 0.31 nM (SYK)[1]
Syk (spleen tyrosine kinase). Syk-IN-4 is a selective Syk inhibitor with an IC50 of 0.31 nM. It blocks immune receptor signaling (e.g., B-cell receptor, Fc receptor) by inhibiting Syk kinase activity, thereby reducing downstream pathways (e.g., NF-kappaB, MAPK, PI3K/AKT). |
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| ln Vitro |
Syk-IN-4 is a strong inhibitor of hERG with an IC50 of 3.0 μM[1]. Syk-IN-4 suppresses SUDHL-4 and T cell proliferation with GI50s of 0.24 and 2.6 μM, respectively[1].
Syk-IN-4 is a potent, selective, and orally bioavailable Syk inhibitor with an IC50 of 0.31 nM. It blocks immune receptor signaling in B cells and myeloid cells, inhibiting activation of downstream pathways including NF-kappaB, MAPK (p38, ERK, JNK), and PI3K/AKT. It reduces proliferation of Syk-dependent B-cell lymphoma lines and inhibits pro-inflammatory cytokine production in immune cells. |
| ln Vivo |
When given orally (1 mg/kg), Syk-IN-4 has a moderate oral bioavailability (60%) in male Hans Wistar rats[1]. In male Hans Wistar rats, Syk-IN-4 shows significant plasma clearance (151 mL/min/kg) and huge volumes of distribution (1.0 L/kg, respectively) after intravenous injection (0.5 mg/kg)[1].
Syk-IN-4 has potential for in vivo efficacy in models of autoimmunity (e.g., rheumatoid arthritis, systemic lupus erythematosus) and hematological cancers (e.g., B-cell lymphomas, acute myeloid leukemia). While specific published in vivo data are not provided, Syk-IN-4 is described as suitable for in vivo studies due to its oral bioavailability. It is expected to reduce autoantibody production and joint inflammation in CIA models and to induce tumor regression in xenograft models of Syk-dependent hematological malignancies. |
| Enzyme Assay |
Cell-free Syk kinase activity assays are performed using recombinant human Syk enzyme. The enzyme is incubated with a peptide substrate and ATP in the presence of increasing concentrations of Syk-IN-4 (0.0001-10,000 nM) in assay buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT). After 30-60 min at 30degC, the reaction is terminated, and IC50 (0.31 nM) is determined by measuring phosphorylated substrate via luminescence (ADP-Glo) or 33P incorporation. Selectivity is assessed against other kinases, including other SYK family members and other protein kinases.
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| Cell Assay |
Syk-dependent B-cell lines (e.g., Ramos, Raji, SU-DHL-4) or primary B cells are seeded in 96-well plates and treated with Syk-IN-4 at various concentrations (0.001-1000 nM) for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. B-cell receptor (BCR) signaling is stimulated with anti-IgM antibody in the presence or absence of Syk-IN-4. Syk inhibition is assessed by measuring phosphorylation of Syk substrates (e.g., BLNK, SLP-65) and downstream signaling pathways (pERK, pAKT, p38) by Western blot or phospho-flow cytometry. Apoptosis is measured by Annexin V/PI staining. IC50 for growth inhibition is determined. For cytokine production, monocytes or macrophages are stimulated with LPS or immune complexes, and TNF-alpha, IL-6, and IL-1beta are measured by ELISA.
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| Animal Protocol |
For in vivo studies, Syk-IN-4 is administered orally to mice (e.g., C57BL/6 or BALB/c) at doses of 1-30 mg/kg once or twice daily. Formulation: 0.5% methylcellulose or 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline. Efficacy studies: collagen-induced arthritis (CIA) model in DBA/1 mice; Syk-IN-4 is administered daily from day 21 post-immunization for 2-3 weeks. Clinical arthritis scores and paw swelling are measured. Serum anti-collagen antibodies and cytokine levels (TNF-alpha, IL-6) are measured by ELISA. Joint histology is performed. For oncology models, mice bearing xenografts of Syk-dependent B-cell lymphoma lines are treated with Syk-IN-4 orally daily for 2-3 weeks. Tumor volumes are measured with calipers. Tumor Syk phosphorylation and downstream signaling are assessed by Western blot.
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| ADME/Pharmacokinetics |
No specific PK data are reported for Syk-IN-4. The molecular weight is 419.48 (C21H25N9O). CAS 2932264-95-2. The compound is described as orally bioavailable, indicating good oral absorption. Solubility: DMSO (>10 mg/mL). Storage: powder at -20degC (3 years) or 4degC (2 years); in solvent at -80degC (6 months) or -20degC (1 month). PK parameters (t1/2, Cmax, AUC) have not been characterized. In vivo formulation is typically done using 0.5% methylcellulose or co-solvent mixtures.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for Syk-IN-4. As a potent Syk inhibitor, potential toxicities include immunosuppression (increased risk of infection), gastrointestinal effects, and hematological toxicities (thrombocytopenia, neutropenia) due to Syk‘s role in platelet function and myeloid cell development. Comprehensive toxicological assessments (hERG, Ames, repeat-dose toxicity in rodents and dogs) have not been published. No clinical trials have been conducted. Not FDA-approved. For research use only.
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| References | |
| Additional Infomation |
Other information: Syk-IN-4 (CAS 2932264-95-2) is a research compound, not FDA-approved. It is a potent, selective, and orally bioavailable Syk inhibitor with an IC50 of 0.31 nM. It is a valuable tool for studying Syk-mediated immune cell signaling in autoimmune diseases (rheumatoid arthritis, SLE) and hematological cancers (B-cell lymphomas, AML). Purity ≥98%. For research use only.
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| Molecular Formula |
C21H25N9O
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|---|---|
| Molecular Weight |
419.482902288437
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| Exact Mass |
419.218
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| CAS # |
2932264-95-2
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| PubChem CID |
154573768
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| Appearance |
White to off-white solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
620
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NN(C=C1CN(C)C)C2=NC(=NC=C2)NC3=CC4=C(C=C3)N(N=C4C(=O)NC)C
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| InChi Key |
IXNQUCOVJRJRGJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H25N9O/c1-13-14(11-28(3)4)12-30(26-13)18-8-9-23-21(25-18)24-15-6-7-17-16(10-15)19(20(31)22-2)27-29(17)5/h6-10,12H,11H2,1-5H3,(H,22,31)(H,23,24,25)
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| Chemical Name |
5-[[4-[4-[(dimethylamino)methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-N,1-dimethylindazole-3-carboxamide
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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: 62.5 mg/mL (148.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.96 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 20.8 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: 2.08 mg/mL (4.96 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 20.8 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: ≥ 2.08 mg/mL (4.96 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 | 2.3839 mL | 11.9195 mL | 23.8390 mL | |
| 5 mM | 0.4768 mL | 2.3839 mL | 4.7678 mL | |
| 10 mM | 0.2384 mL | 1.1920 mL | 2.3839 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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