| Targets |
CCR6 inhibitor 1 targets the C-C chemokine receptor type 6 (CCR6), a G protein-coupled receptor that is predominantly expressed on immune cells, including T-cells, B-cells, and dendritic cells. Its primary ligand is CCL20 (macrophage inflammatory protein-3 alpha). The CCL20/CCR6 axis plays a critical role in the recruitment of immune cells to sites of inflammation and is implicated in the pathogenesis of various autoimmune diseases, such as psoriasis and inflammatory bowel disease, as well as in tumor progression.
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| ln Vitro |
CCR6 inhibitor 1 (compound 35) prevents human B cells from migrating in response to L20 [1].
In vitro, CCR6 inhibitor 1 demonstrates exceptionally potent and selective inhibition of CCR6. It has IC50 values of 0.45 nM for monkey CCR6 and 6 nM for human CCR6. It displays remarkable selectivity over related receptors, with an IC50 of >30,000 nM for human CCR1 and 9,400 nM for CCR7. In functional assays using human CCR6-transfected CHO cells, it shows a good correlation between Gi signal inhibitory activity and cell migration inhibitory activity. It markedly blocks ERK phosphorylation and effectively inhibits CCR6-dependent cell migration in human primary cells. |
| ln Vivo |
In vivo, CCR6 inhibitor 1 is used to study the role of CCR6 in disease models. Its ability to inhibit immune cell migration and inflammatory responses makes it a useful tool for investigating the pathophysiology of autoimmune and inflammatory diseases. It can be administered in animal models to assess its effect on disease severity and immune cell infiltration.
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| Enzyme Assay |
The inhibitory activity of CCR6 inhibitor 1 is assessed using cell-based functional assays, such as calcium mobilization or chemotaxis assays. Cells expressing CCR6 (e.g., transfected CHO cells or primary human cells) are treated with varying concentrations of the compound and then stimulated with the ligand CCL20. The reduction in intracellular calcium flux or cell migration is measured, and the IC50 is calculated from the dose-response curve. Receptor binding assays can also be used to assess its affinity.
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| Cell Assay |
The cellular activity of CCR6 inhibitor 1 is evaluated in CCR6-expressing cell lines and primary immune cells. Cells are treated with the compound, and its effect on CCL20-induced signaling pathways, such as ERK phosphorylation, is measured by Western blot. Its ability to inhibit CCR6-dependent cell migration is assessed using transwell migration assays. The compound's selectivity is confirmed by testing it against other chemokine receptors.
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| Animal Protocol |
In animal studies, CCR6 inhibitor 1 is typically administered to rodents via oral gavage or intraperitoneal injection. In models of autoimmune diseases (e.g., experimental autoimmune encephalomyelitis or colitis), its effect on disease severity, inflammatory markers, and immune cell infiltration into target tissues is assessed. In cancer models, it is used to study the role of CCR6 in tumor progression and metastasis.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of CCR6 inhibitor 1 are not extensively documented in public sources. As a small molecule (MW 504.5), it is expected to have moderate oral bioavailability. Its solubility and formulation would need to be optimized for in vivo studies. However, its use in preclinical models suggests it has suitable properties for research applications.
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| Toxicity/Toxicokinetics |
Toxicology data for CCR6 inhibitor 1 is limited, as it is a research compound not intended for human use. Its safety profile has not been established in formal toxicology studies. However, its potent and specific mechanism of action suggests that on-target effects related to immune modulation would be the primary concern.
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| References | |
| Additional Infomation |
CCR6 inhibitor 1 (CAS: 2437547-04-9) is a highly potent and selective chemical probe for studying CCR6 biology. Its exceptional potency (IC50 = 6 nM for human CCR6) and selectivity over other chemokine receptors make it an invaluable tool for dissecting the role of the CCL20/CCR6 axis in health and disease. It is used in research on autoimmune diseases and cancer. Its development represents a significant advancement in the field of chemokine receptor pharmacology.
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| Exact Mass |
504.144
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|---|---|
| CAS # |
2437547-04-9
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| PubChem CID |
134817249
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| Appearance |
White to off-white solid powder
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| Density |
1.391±0.06 g/cm3(Predicted)
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| Boiling Point |
705.4±60.0 °C(Predicted)
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
819
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CNOZLNNAVQPFBD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H23F3N4O3S/c25-24(26,27)17-3-10-22(30-14-17)31-18-4-8-20(9-5-18)35(33,34)19-6-1-15(2-7-19)16-11-12-29-21(13-16)23(28)32/h1-3,6-7,10-14,18,20H,4-5,8-9H2,(H2,28,32)(H,30,31)
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| Chemical Name |
4-[4-[4-[[5-(trifluoromethyl)pyridin-2-yl]amino]cyclohexyl]sulfonylphenyl]pyridine-2-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 : ≥ 125 mg/mL (~247.76 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.12 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 (4.12 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 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 (4.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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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