| Size | Price | Stock | Qty |
|---|---|---|---|
| 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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| 250mg |
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| Other Sizes |
| Targets |
CCR8 ( Ki = 1.6 nM )
Human CCR8 (Chemokine Receptor 8) – antagonist (FMAT Ki = 57 nM, FLIPR IC50 = 150 nM)[1] |
|---|---|
| ln Vitro |
CCR8 binding affinity: Compound 1 exhibited binding affinity to human CCR8 with a Ki of 57 nM in the FMAT binding assay and an IC50 of 150 nM in the FLIPR calcium mobilization assay.[1]
- Selectivity: Selected compounds (e.g., 15) showed >300-fold selectivity against a panel of GPCRs, including other chemokine receptors (<20% inhibition at 10 µM in the Novascreen panel).[1] - hERG binding: Compound 15 did not show significant hERG binding in HEK293 cells (Ki > 10 µM).[1] - P450 inhibition: The compounds did not significantly inhibit cytochrome P450 isozymes, including CYP3A4 (IC50 > 10 µM).[1] |
| Cell Assay |
FLIPR Calcium Mobilization Assay: CHO/Ga16 cells stably expressing human CCR8 were plated in 384-well plates and loaded with Fluo-3. Cells were pre-incubated with antagonists or DMSO, then stimulated with CCL1 (2 nM). Intracellular Ca²⁺ flux was measured using a FLIPR reader. Antagonist IC50 values were calculated from inhibition of CCL1-induced Ca²⁺ increase.[1]
- FMAT Binding Assay: L1.2/hCCR8 cells were suspended in binding buffer. A mixture of biotinylated human CCL1 and Cy5-labeled anti-biotin antibody was added along with test compounds. After incubation, fluorescence was measured on an FMAT system. Binding affinity (Ki) was determined by competition with labeled CCL1.[1] |
| ADME/Pharmacokinetics |
Oral bioavailability: The oral bioavailability of compound 15 is low to moderate: 2% in rats and 10% in dogs. [1] - Half-life (t½): The t½ of compound 15 is 2.6 hours in rats and 3.7 hours in dogs. [1] - Volume of distribution (Vss): The Vss of compound 15 is 1.6 L/kg in rats and 1.5 L/kg in dogs. [1] - Clearance (CL): The CL of compound 15 is 1.4 L/h/kg in rats and 0.42 L/h/kg in dogs. [1] - Metabolic stability: Some early lead compounds (e.g., 6 g) show rapid amide cleavage in rodent plasma (mouse plasma t½ = 0.5 hours), which can be improved by structural modification (e.g., 15, mouse plasma t½ = 8.2 hours). h).[1]
- Caco-2 cell permeability: Some compounds (e.g., 15 and 14b) showed acceptable efflux ratios (~1.3), while others (e.g., 33c) showed higher efflux ratios (ratio = 11), indicating potential P-gp substrate properties. [1] - Hepatic clearance: In vitro microsomal stability studies showed that amide 14b and urea 33c had better hepatic stability than carbamate 15. [1] |
| Toxicity/Toxicokinetics |
hERG binding: No significant binding was observed in compound 15 (Ki > 10 µM). [1]
P450 inhibition: No significant inhibition of major CYP isoenzymes was observed (IC50 > 10 µM). [1] |
| References | |
| Additional Infomation |
Chemical Classification: Naphthalenesulfonamides are small molecule CCR8 antagonists. [1]
- Therapeutic Indications: Based on CCR8 expression patterns, they are intended for the treatment of diseases mediated by CCR8-CCL1 interactions, such as allergic asthma, multiple sclerosis, and cancer. [1] - Mechanism: Antagonizes the activation of CCR8 by endogenous ligand CCL1, inhibiting downstream signaling (e.g., calcium mobilization). [1] - Structure-Activity Relationship Study: Amide NH and sulfonamide NH are crucial for efficient binding to CCR8. The left-side amide group is resistant to a variety of hydrophobic groups, while the right-side amide group is more inclined to piperidine-derived sulfonamides with urethane, urea, or amide substituents. [1] - Future Studies: This paper focuses on structure-activity relationship and in vitro analysis; in vivo optimization and pharmacokinetic improvements will be discussed in subsequent reports. [1] |
| Molecular Formula |
C26H29N3O5S
|
|---|---|
| Molecular Weight |
495.59
|
| Exact Mass |
495.18
|
| Elemental Analysis |
C, 63.01; H, 5.90; N, 8.48; O, 16.14; S, 6.47
|
| CAS # |
723304-76-5
|
| PubChem CID |
16105788
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.2
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
35
|
| Complexity |
836
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
LGJRRERRFSZFTJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H29N3O5S/c1-3-34-26(31)29-16-14-19(15-17-29)28-35(32,33)24-13-12-23(21-10-6-7-11-22(21)24)27-25(30)20-9-5-4-8-18(20)2/h4-13,19,28H,3,14-17H2,1-2H3,(H,27,30)
|
| Chemical Name |
ethyl 4-[[4-[(2-methylbenzoyl)amino]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxylate
|
| Synonyms |
LUN-04765; LUN 04765; CCR8 antagonist 1; LUN04765
|
| 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)
|
| Solubility (In Vitro) |
DMSO: ~25 mg/mL (~50.4 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0178 mL | 10.0890 mL | 20.1780 mL | |
| 5 mM | 0.4036 mL | 2.0178 mL | 4.0356 mL | |
| 10 mM | 0.2018 mL | 1.0089 mL | 2.0178 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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