| 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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| Other Sizes |
| Targets |
CCR8 (chemokine receptor 8).
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|---|---|
| ln Vitro |
In a cell line that stably expresses cynomolgus monkey CCR8, ML604086 (0-100 μM) has IC50 values of 1.3 μM and 1.0 μM, respectively, which inhibit CCL1-mediated chemotaxis and raise intracellular Ca2+ concentration [2]. CCR8 on CCL1 and CD4 T cells is inhibited by ML604086 (10, 30 μM; 64 h). Adsorbed solution 5HT1a showed 30% and 70% inhibition rates at 10 and 30 μM, respectively [2].
ML604086 is a selective CCR8 antagonist that inhibits CCL1 binding to CCR8 on circulating T-cells. It inhibits CCL1-mediated chemotaxis with an IC50 of 1.3 µM and inhibits CCL1-induced increases in intracellular Ca2+ concentrations with an IC50 of 1.0 µM in cellular assays. The compound displays high selectivity against a panel of 40 GPCRs, only moderately inhibiting 5HT1a (30% at 10 µM). ML604086 is used for research in immunomodulation and autoimmune diseases. |
| ln Vivo |
Cynomolgus monkeys' airway acidic eosinophil growth, generation of proinflammatory cytokines, airway blockage, and compliance are all unaffected by ML604086 (1.038 mg/kg; intravenous cell infusion) [1].
In vivo efficacy data for ML604086 is limited. The compound is primarily used as an in vitro tool for studying CCR8 biology and its role in immune cell trafficking and autoimmune diseases. As a CCR8 antagonist, it has potential applications in modulating T-cell migration and treating autoimmune conditions. Further in vivo studies in animal models of autoimmune diseases would be needed to assess its therapeutic potential. |
| Enzyme Assay |
The in vitro receptor binding assay for CCR8 antagonism uses membrane preparations from cells expressing recombinant human CCR8. ML604086 is incubated with the receptor preparation and a radiolabeled CCR8 ligand (e.g., [125I]CCL1) at varying concentrations (typically 0.01 nM to 100 µM). After incubation, bound and free radioactivity are separated by filtration. The IC50 or Ki is calculated from competition binding curves. Selectivity is assessed by profiling against a panel of 40 GPCRs.
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| Cell Assay |
In vitro cellular assays are performed using cells expressing CCR8 (e.g., circulating T-cells or recombinant cell lines). Cells are treated with ML604086 at concentrations ranging from 0.01 to 100 µM for 30-60 minutes, then stimulated with CCL1. Chemotaxis is assessed using Transwell migration assays. Intracellular Ca2+ concentrations are measured using calcium-sensitive fluorescent dyes (e.g., Fluo-4). The IC50 for inhibition of chemotaxis and Ca2+ flux is calculated from dose-response curves. Selectivity is confirmed by profiling against a panel of GPCRs.
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| Animal Protocol |
Animal/Disease Models: 3.0-5.0 kg male and female adult macaques (primate asthma model) [2]
Doses: 1.038 mg/kg Route of Administration: intravenous (iv) (iv)infusion Experimental Results: Does not affect allergen challenge and increased concentration of methacholine changes in airway resistance and compliance. In vivo animal model data for ML604086 is not extensively reported in the literature. As a research tool for studying CCR8 biology in immunomodulation and autoimmune diseases, the compound would typically be evaluated in mouse models of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) or collagen-induced arthritis. Standard efficacy studies would involve compound administration (oral or intraperitoneal) followed by assessment of disease severity, immune cell infiltration, and inflammatory cytokine levels. Pharmacokinetic studies would assess oral bioavailability, plasma half-life, and tissue distribution. |
| ADME/Pharmacokinetics |
ML604086 has a molecular weight of 508.63 g/mol. It is soluble in DMSO and should be stored as a powder at -20°C. Pharmacokinetic parameters such as oral bioavailability, plasma half-life, and tissue distribution are not extensively characterized in publicly available literature. As a research compound, it is typically used in in vitro assays at concentrations ranging from nanomolar to low micromolar.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available for ML604086. As a research compound, it is not intended for human use and has not undergone formal toxicological evaluation. Standard preclinical safety assessments for CCR8 antagonists would typically include selectivity profiling against a panel of GPCRs to assess off-target effects, hERG channel inhibition for cardiac safety, and CYP450 enzyme inhibition for drug-drug interaction potential. The compound is supplied as a solid and should be stored desiccated at -20°C.
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| References | |
| Additional Infomation |
ML604086 is a research-grade CCR8 antagonist that inhibits CCL1-mediated chemotaxis and Ca2+ flux. It is not approved for clinical use. The compound displays high selectivity against a panel of 40 GPCRs. ML604086 is used for research in immunomodulation and autoimmune diseases. It is supplied as a solid with high purity and should be stored desiccated at -20°C.
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| Molecular Formula |
C27H32N4O4S
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|---|---|
| Molecular Weight |
508.632385253906
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| Exact Mass |
508.214
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| CAS # |
850330-18-6
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| PubChem CID |
57564362
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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 |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
891
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| Defined Atom Stereocenter Count |
3
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| SMILES |
S(C1=CC=C(NC(C2C=CC=CC=2C)=O)C2C=CC=CC1=2)(=O)(=O)N[C@@H]1CCN(C(=O)[C@@H](N)C)C[C@H]1C
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| InChi Key |
FABRBEGQMXBELT-SELNLUPBSA-N
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| InChi Code |
InChI=1S/C27H32N4O4S/c1-17-8-4-5-9-20(17)26(32)29-24-12-13-25(22-11-7-6-10-21(22)24)36(34,35)30-23-14-15-31(16-18(23)2)27(33)19(3)28/h4-13,18-19,23,30H,14-16,28H2,1-3H3,(H,29,32)/t18-,19+,23-/m1/s1
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| Chemical Name |
N-[4-[[(3R,4R)-1-[(2S)-2-aminopropanoyl]-3-methylpiperidin-4-yl]sulfamoyl]naphthalen-1-yl]-2-methylbenzamide
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| Synonyms |
ML 604086 ML-604086 ML604086
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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 : ~120 mg/mL (~235.93 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (12.29 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 62.5 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: ≥ 6.25 mg/mL (12.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9661 mL | 9.8303 mL | 19.6607 mL | |
| 5 mM | 0.3932 mL | 1.9661 mL | 3.9321 mL | |
| 10 mM | 0.1966 mL | 0.9830 mL | 1.9661 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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