| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
CCR2 (C-C chemokine receptor type 2). (1S)-CCR2 antagonist 1 is a high-affinity, long-residence-time CCR2 antagonist with a Ki of 2.4 nM. It blocks the binding of chemokines (e.g., CCL2/MCP-1) to CCR2, thereby inhibiting downstream signaling pathways involved in monocyte chemotaxis and activation.
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| ln Vitro |
The hit-to-lead procedure utilizing both SAR and SKR leads to the identification of a novel CCR2 antagonist with higher affinity and longer half-life (CCR2 antagonist 1 (compound 15a), Ki=2.4 nM; RT=714 min)[1].
In vitro, (1S)-CCR2 antagonist 1 binds to CCR2 with a Ki of 2.4 nM, demonstrating high affinity. It exhibits an exceptionally long residence time (RT = 714 min) on the receptor, which contributes to sustained pharmacological activity in cell-based assays. At nanomolar concentrations, it effectively inhibits MCP-1-induced calcium flux and chemotaxis in CCR2-expressing cells. |
| ln Vivo |
No detailed in vivo studies are publicly available for the isolated (1S)-enantiomer. The racemic CCR2 antagonist 1 has demonstrated efficacy in rodent models of inflammatory diseases, including reduced monocyte infiltration and attenuated disease severity in models of multiple sclerosis (EAE) and rheumatoid arthritis (CIA).
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| Enzyme Assay |
Binding affinity and kinetics (Ki and residence time) are measured using a radioligand binding assay with membranes from CCR2-expressing cells. Membranes are incubated with [125I]-MCP-1 or a tritiated CCR2 antagonist in the presence of serial dilutions of (1S)-CCR2 antagonist 1 (0.1-1000 nM). Bound radioactivity is measured by filtration and scintillation counting. Residence time (RT) is determined by dissociation kinetic experiments.
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| Cell Assay |
For in vitro functional assays, CCR2-expressing cells (e.g., THP-1 monocytes or primary human monocytes) are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4). Cells are pre-incubated with serial dilutions of (1S)-CCR2 antagonist 1 (0.1-1000 nM) for 15-30 minutes, then stimulated with MCP-1/CCL2 (e.g., 10 nM). Calcium flux is measured by fluorescence spectrophotometry. Chemotaxis is assessed using transwell chambers with MCP-1 in the lower chamber.
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| Animal Protocol |
No dedicated in vivo studies are reported for (1S)-CCR2 antagonist 1 alone. For research use, a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) can be used. Mice are immunized with MOG peptide in CFA. (1S)-CCR2 antagonist 1 is administered orally or intraperitoneally at 3-30 mg/kg daily. Clinical EAE scores are monitored, and spinal cord tissues are harvested for histopathological analysis of immune cell infiltration.
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| ADME/Pharmacokinetics |
(1S)-CCR2 antagonist 1 has a molecular weight of 549.47 g/mol and a formula of C28H32BrF3N2O. It is soluble in DMSO (125 mg/mL). Its high lipophilicity (LogP >4) suggests excellent membrane permeability and potential for good oral bioavailability. Detailed PK parameters are not publicly available but are consistent with the racemic form.
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| Toxicity/Toxicokinetics |
Detailed toxicological data are not publicly available. Based on the safety profile of other CCR2 antagonists, potential adverse effects may include mild immunosuppression and increased susceptibility to infections due to reduced monocyte trafficking. No significant organ toxicity has been reported for the racemic compound at therapeutic doses.
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| References | |
| Additional Infomation |
(1S)-CCR2 antagonist 1 is a research-grade compound not approved for clinical use. It is the isolated left-handed chiral form of CCR2 antagonist 1 (compound 15a), described in the literature (Eur J Med Chem. 2015 Mar 26;93:121-34). It is used to study the role of CCR2 in monocyte recruitment and to explore the therapeutic potential of CCR2 antagonism in autoimmune and inflammatory diseases.
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| Molecular Formula |
C28H32BRF3N2O
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|---|---|
| Molecular Weight |
549.465697288513
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| Exact Mass |
548.165
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| CAS # |
1683534-97-5
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| Related CAS # |
CCR2 antagonist 1;1683534-96-4
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| PubChem CID |
118734690
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
776
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC(C)[C@@]1(CC[C@H](C1)N[C@H]2CCC3=C2C=CC(=C3)Br)C(=O)N4CCC5=C(C4)C=C(C=C5)C(F)(F)F
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| InChi Key |
QYDUEIJZRKTNKN-NIYJGHKDSA-N
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| InChi Code |
InChI=1S/C28H32BrF3N2O/c1-17(2)27(11-9-23(15-27)33-25-8-4-19-14-22(29)6-7-24(19)25)26(35)34-12-10-18-3-5-21(28(30,31)32)13-20(18)16-34/h3,5-7,13-14,17,23,25,33H,4,8-12,15-16H2,1-2H3/t23-,25+,27+/m1/s1
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| Chemical Name |
[(1S,3R)-3-[[(1S)-5-bromo-2,3-dihydro-1H-inden-1-yl]amino]-1-propan-2-ylcyclopentyl]-[7-(trifluoromethyl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| 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 | 1.8199 mL | 9.0997 mL | 18.1994 mL | |
| 5 mM | 0.3640 mL | 1.8199 mL | 3.6399 mL | |
| 10 mM | 0.1820 mL | 0.9100 mL | 1.8199 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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