| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
SYK (Spleen tyrosine kinase).
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|---|---|
| ln Vitro |
In RBL-2H3 cells, tumor peritoneum, and human cultured mast cells, ER-27319 (24 h) decreases the formation of inositol phosphate, the release of arachidonic acid, histamine, and tumor cytokine alpha. Around 10 μM is the approximate value at which the ER-27319 (10-30 μM, 10 min) loop suppresses the tyrosine phosphorylation of SYK caused by the immunoreceptor tyrosine activation motif of FcεRI γ [1]. The tyrosine phosphorylation of ZAP-70 in Jurkat cells caused by CD3 stimulation is not inhibited by ER-27319 (up to 100 μM, 60 min) [1]. Anti-IgG-stimulated canine skin tumor-derived mast cells exhibit decreased tyrosine phosphorylation of two proteins (62, 80 kD) and inhibition of two other proteins (38, 70 kD) upon exposure to ER-27319 (100 μM, 10 min).
ER-27319 inhibits SYK activation with an IC50 of approximately 10 uM in cell-based assays; it inhibits antigen- or anti-IgE-mediated degranulation of rodent and human mast cells; it prevents the phosphorylated ITAM domain of FcεRI gamma from activating SYK but does not inhibit previously activated SYK; it does not inhibit SYK phosphorylation in B cells. |
| ln Vivo |
Not fully detailed; based on its mechanism, ER-27319 is expected to show efficacy in mouse models of allergic diseases such as passive cutaneous anaphylaxis (PCA) or ovalbumin-induced asthma; specific in vivo efficacy data are not extensively reported in open sources.
|
| Enzyme Assay |
Binding inhibition is measured by assessing SYK's interaction with the ITAM domain; a cell-free assay is performed using recombinant SYK protein and a biotinylated ITAM-containing peptide derived from FcεRI gamma; after incubation with ER-27319, the peptide-SYK interaction is detected by ELISA or fluorescence polarization; inhibition of SYK phosphorylation is measured by Western blot using anti-phospho-SYK antibodies.
|
| Cell Assay |
Western Blot Analysis [1]
Cell Types: RBL-2H3 Cell Tested Concentrations: 10, 30 and 100 μM Incubation Duration: 10 minutes Experimental Results: Inhibition of tyrosine phosphorylation of SYK in mast cells (57% inhibition at 10 and 30 μM, respectively and 87%). Inhibits SYK tyrosine phosphorylation induced by the phospho-γ ITAM of FcεRI γ but not the phospho-Ig β immunoreceptor tyrosine activation motif at 10 and 30 μM . 100 μM has no effect on SYK phosphorylation induced by the Igβ immunoreceptor tyrosine activation motif. Western Blot Analysis[1] Cell Types: Jurkat cells Tested Concentrations: 3, 10, 30, 100 μM Incubation Duration: 10, 30, 60 minutes Experimental Results: ID does not inhibit tyrosine phosphorylation of ZAP-70 in response to anti-CD3 stimulation. Mast cell degranulation assays: rat basophilic leukemia (RBL-2H3) cells or primary human mast cells are sensitized with IgE (overnight), then treated with ER-27319 (10-30 uM, 10 minutes) followed by antigen stimulation (e.g., DNP-BSA); degranulation is measured by release of beta-hexosaminidase or histamine; SYK phosphorylation is analyzed by immunoblotting. |
| Animal Protocol |
Mouse models of passive cutaneous anaphylaxis: mice are sensitized intradermally with IgE antibodies, followed by intravenous administration of antigen (e.g., DNP-BSA) together with Evans blue dye; ER-27319 is administered prior to challenge; extravasated dye in ear or skin tissue is extracted and quantified spectrophotometrically.
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| ADME/Pharmacokinetics |
PK properties not fully detailed; as a small-molecule acridone derivative, limited information on absorption, half-life, and metabolism; further ADME studies would be required for preclinical development; no published human PK data available.
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| Toxicity/Toxicokinetics |
Toxicity profile not fully characterized; as an experimental research compound, no systematic toxicity studies have been reported; based on its mechanism targeting SYK, potential immunomodulatory effects might be expected; no clinical safety data are available.
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| References |
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| Additional Infomation |
ER-27319 is a research-use only compound for studying SYK-mediated signaling in allergic and inflammatory responses; it is not approved for clinical use; no clinical trials have been registered; it serves as a chemical probe for investigating the role of SYK in mast cell activation, anaphylaxis, and other immune-mediated disorders.
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| Molecular Formula |
C20H22N2O5
|
|---|---|
| Molecular Weight |
396.43636
|
| Exact Mass |
396.169
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| CAS # |
201010-95-9
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| Related CAS # |
ER-27319 maleate;1204480-26-1
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| PubChem CID |
9799508
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.149g/cm3
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| Boiling Point |
475.894ºC at 760 mmHg
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| Flash Point |
241.613ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.611
|
| LogP |
3.532
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
455
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C2=C(C=CC=C2)N(CCCN)C3=C(C)C(C)=CC=C13.O=C(O)C(O)=O
|
| InChi Key |
IIELZHYJYZBSGG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H20N2O.C2H2O4/c1-12-8-9-15-17(13(12)2)20(11-5-10-19)16-7-4-3-6-14(16)18(15)21;3-1(4)2(5)6/h3-4,6-9H,5,10-11,19H2,1-2H3;(H,3,4)(H,5,6)
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| Chemical Name |
10-(3-aminopropyl)-3,4-dimethylacridin-9-one;oxalic acid
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: ~50 mg/mL (~135.0 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (6.75 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL | |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL | |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 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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