| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
ZAP-180013 targets ZAP-70 (zeta-chain-associated protein kinase 70), a key tyrosine kinase involved in T-cell receptor (TCR) signaling. ZAP-70 is essential for T-cell activation and function. By inhibiting the interaction of the ZAP-70 SH2 domain with ITAMs (immunoreceptor tyrosine-based activation motifs), ZAP-180013 prevents ZAP-70 recruitment to the TCR and subsequent downstream signaling. This mechanism makes it a valuable tool for studying TCR signaling and immune modulation.
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| ln Vitro |
The molecule ZAP-70 plays a crucial role in both T cell activation and signal transduction during T cell acquisition. When T cell acquisition is activated, ZAP-70 is drawn to the intracellular z chain, where it colocalizes with the substrate and becomes activated. ZAP-70 may be used in organ transplant or autoimmune treatments. ZAP-180013 breaks the link between ZAP-70 and T cell receptors; its IC50 values in FP and TR-FRET assays are 9.6 μM and 16.841 μM, respectively [1].
In vitro, ZAP-180013 inhibits ZAP-70 with an IC50 of 1.8 μM. The compound inhibits the interaction of the ZAP-70 SH2 domain with ITAMs. ZAP-180013 also effectively inhibits inflammasome activation in human myeloid cells, including those carrying MCC950-resistant NLRP3 mutations. These in vitro studies demonstrate the compound's potential for studying T-cell signaling and inflammasome biology. |
| ln Vivo |
In vivo, ZAP-180013 has been shown to ameliorate psoriasiform skin inflammation and protect against lipopolysaccharide (LPS)-induced cytokine responses in mice. These in vivo studies demonstrate the compound's potential for studying immune-mediated diseases and developing therapeutic strategies for autoimmunity and inflammation.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for ZAP-180013 measures its ability to inhibit ZAP-70 kinase activity or ZAP-70 SH2 domain binding to ITAMs. Kinase assays are performed using purified ZAP-70 and peptide substrates, with phosphorylation detected by radioactive or fluorescence-based methods. Binding assays measure the inhibition of ZAP-70 SH2 domain interaction with phosphorylated ITAM peptides using ELISA, surface plasmon resonance, or fluorescence polarization. IC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cellular studies are conducted using T cells or other immune cells. Cells are treated with ZAP-180013 at various concentrations (typically μM ranges) for defined time periods. T-cell activation is measured by assessing proliferation, cytokine production (e.g., IL-2), and surface marker expression. Inflammasome activation is studied in myeloid cells by measuring IL-1β and IL-18 secretion, caspase-1 activation, and NLRP3 inflammasome assembly. Cell viability is assessed using standard cytotoxicity assays.
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| Animal Protocol |
In vivo animal experiments are performed using models of immune-mediated diseases. For psoriasiform skin inflammation models, mice are administered ZAP-180013 via various routes at different doses. Skin inflammation is assessed by clinical scores, histopathology, and measurement of inflammatory markers. For LPS-induced cytokine response models, mice are treated with ZAP-180013 before LPS challenge, and serum cytokine levels are measured. These studies evaluate the compound's in vivo efficacy and mechanism.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ZAP-180013 include solubility in DMSO (250 mg/mL). The compound has a molecular weight of 454.33 g/mol and molecular formula C19H17Cl2N3O4S. For in vivo administration, formulations such as 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline (5 mg/mL) are recommended. Storage conditions should follow the certificate of analysis. The compound should be protected from light and moisture.
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| Toxicity/Toxicokinetics |
Toxicological data for ZAP-180013 are derived from preclinical studies. The compound is for research use only and not intended for human therapeutic applications. No significant toxicity has been reported at effective doses in animal studies. Standard safety precautions should be followed when handling the compound due to its potent biological activity. Long-term toxicity and carcinogenicity studies have not been conducted.
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| References | |
| Additional Infomation |
ZAP-180013 is an inhibitor of zeta-chain-associated protein kinase 70 (ZAP-70) with an IC50 of 1.8 μM. It inhibits the interaction of the ZAP-70 SH2 domain with ITAMs. The compound is used in immunology and pharmacological research to dissect TCR signaling mechanisms and evaluate kinase inhibition as a strategy for therapeutic immune modulation. It also effectively inhibits inflammasome activation in human myeloid cells. The compound has the molecular formula C19H17Cl2N3O4S and molecular weight of 454.33 g/mol.
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| Molecular Formula |
C19H17CL2N3O4S
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| Molecular Weight |
454.326981306076
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| Exact Mass |
453.031
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| CAS # |
873080-25-2
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| PubChem CID |
2988718
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
652
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N(CC1C=CC(Cl)=CC=1)CC1=CC=CO1)C1C(Cl)=CN=C(S(CC)(=O)=O)N=1
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| InChi Key |
GTWKIPDKVRLUKN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17Cl2N3O4S/c1-2-29(26,27)19-22-10-16(21)17(23-19)18(25)24(12-15-4-3-9-28-15)11-13-5-7-14(20)8-6-13/h3-10H,2,11-12H2,1H3
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| Chemical Name |
5-Chloro-N-[(4-chlorophenyl)methyl]-2-(ethylsulfonyl)-N-(2-furanylmethyl)-4-pyrimidinecarboxamide
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| Synonyms |
ZAP 180013 ZAP180013 ZAP-180013
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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 : ~250 mg/mL (~550.26 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.58 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 (4.58 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 (4.58 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 | 2.2010 mL | 11.0052 mL | 22.0104 mL | |
| 5 mM | 0.4402 mL | 2.2010 mL | 4.4021 mL | |
| 10 mM | 0.2201 mL | 1.1005 mL | 2.2010 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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