| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
The target is CCR4 (C-C motif chemokine receptor 4), a G-protein-coupled receptor expressed on the surface of Th2 lymphocytes and regulatory T cells (Tregs). By acting as an antagonist, Zelnecirnon blocks the binding of the natural chemokine ligands, CCL22 (MDC) and CCL17 (TARC), thereby preventing the migration of these inflammatory cells into tissues like the skin and lungs.
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| ln Vitro |
Zelnecirnon has an IC50 of about 370 nM and inhibits Th2 cell chemotaxis or migration at concentrations of 1 nM–10 μM[2].
Specific in vitro data for Zelnecirnon is not detailed in the available literature, but as a CCR4 antagonist, its activity is typically measured in chemotaxis assays. It effectively inhibits the migration of CCR4-expressing Th2 cells in response to CCL22 or CCL17. The binding affinity (IC50 or Ki) is determined in radioligand binding assays using CCR4-overexpressing cell membranes. |
| ln Vivo |
A mouse model of acute ovalbumin (OVA)-induced atopic dermatitis has shown that zelnecirnon (100 mg/kg; oral; once daily; 2 days, 1 day before OVA challenge) reduces skin inflammation [2].
Specific in vivo data for Zelnecirnon is not detailed. As an orally active CCR4 antagonist, it is expected to show efficacy in mouse models of atopic dermatitis and asthma. Studies would measure the reduction of Th2 cell infiltration into inflamed tissues, leading to decreased levels of Th2 cytokines (IL-4, IL-5, IL-13). Phase 1b trial data in atopic dermatitis patients has shown marked improvement. |
| Enzyme Assay |
A biochemical assay for CCR4 is a radioligand binding assay. Membranes prepared from cells expressing human CCR4 are incubated with a radiolabeled tracer (e.g., 125I-labeled CCL22) and varying concentrations of Zelnecirnon. After incubation, the mixture is filtered, and the radioactivity retained on the filter is measured by a scintillation counter. The ability of the compound to displace the tracer is used to calculate Ki or IC50.
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| Cell Assay |
A cellular functional assay for CCR4 is a chemotaxis assay using a Transwell system. CCR4-expressing cells (e.g., a cell line or primary human Th2 cells) are placed in the upper chamber. The lower chamber contains the chemoattractants CCL22 or CCL17. Zelnecirnon is added to the cells in the upper chamber. After 2-4 hours of incubation, the number of cells that migrated to the lower chamber is counted by flow cytometry or using a fluorescence plate reader.
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| Animal Protocol |
Animal/Disease Models: Mouse acute ovalbumin (OVA)-induced atopic dermatitis model [2]
Doses: 100 mg/kg Route of Administration: po (oral gavage); one time/day; lasts for 2 days, starting 1 day before OVA challenge (In mouse ears) Experimental Results: Significant reduction in ear thickness. In vivo animal experimental procedures were not detailed in the available literature. A typical protocol for a CCR4 antagonist in asthma would use a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Mice are sensitized with OVA and then challenged with intranasal OVA. Zelnecirnon would be administered orally daily. On the final day, bronchoalveolar lavage (BAL) fluid is collected to count eosinophils and measure Th2 cytokines. Lung tissue is collected for histological analysis of inflammation. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic properties of Zelnecirnon are not detailed in the available literature. However, as it is described as an "orally active" compound in clinical trials, it is designed to have favorable oral bioavailability, metabolic stability, and a suitable half-life for once or twice daily human dosing. Pharmacokinetic data from Phase 1 trials would be available from the manufacturer.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for Zelnecirnon is not provided. However, the compound has completed a Phase 1b trial in atopic dermatitis patients with little side effects, indicating an acceptable safety profile at the therapeutic doses studied. Standard toxicology studies (e.g., single and repeat-dose toxicity in rodents and non-rodents) would have been conducted to support these clinical trials.
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| References |
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| Additional Infomation |
Zelnecirnon is a clinical-stage drug candidate, having completed a Phase 1b trial. The trial, conducted in patients with atopic dermatitis, found that marked improvement occurred after 4 weeks of treatment with little side effects. These results make it a promising therapeutic candidate for treating allergic inflammatory diseases, moving it beyond a simple research reagent and into clinical development.
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| Molecular Formula |
C27H34CL3N5O2
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|---|---|
| Molecular Weight |
566.95
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| Exact Mass |
565.177
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| CAS # |
2366152-15-8
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| PubChem CID |
139344142
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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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 |
7
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| Heavy Atom Count |
37
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| Complexity |
811
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| Defined Atom Stereocenter Count |
2
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| SMILES |
[C@]1(C)(C(O)=O)C[C@@H](N2CCC[C@H](C3CN(C4=NC(C)=C(Cl)C(N[C@@H](C5=CC=C(Cl)C=C5Cl)C)=N4)C3)C2)C1
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| InChi Key |
ANPSFQZLPNWKHR-BPZFHHOVSA-N
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| InChi Code |
InChI=1S/C27H34Cl3N5O2/c1-15(21-7-6-19(28)9-22(21)29)31-24-23(30)16(2)32-26(33-24)35-13-18(14-35)17-5-4-8-34(12-17)20-10-27(3,11-20)25(36)37/h6-7,9,15,17-18,20H,4-5,8,10-14H2,1-3H3,(H,36,37)(H,31,32,33)/t15-,17+,20-,27-/m1/s1
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| Chemical Name |
(1R,3r)-3-((R)-3-(1-(5-chloro-4-(((R)-1-(2,4-dichlorophenyl)ethyl)amino)-6-methylpyrimidin-2-yl)azetidin-3-yl)piperidin-1-yl)-1-methylcyclobutane-1-carboxylic acid
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| Synonyms |
RPT-193 RPT193 ZelnecirnonRPT 193
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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 : ~100 mg/mL (~176.38 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.41 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 25.0 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: ≥ 2.5 mg/mL (4.41 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 25.0 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: ≥ 2.5 mg/mL (4.41 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 | 1.7638 mL | 8.8191 mL | 17.6382 mL | |
| 5 mM | 0.3528 mL | 1.7638 mL | 3.5276 mL | |
| 10 mM | 0.1764 mL | 0.8819 mL | 1.7638 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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