| Size | Price | Stock | Qty |
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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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| Targets |
C-021 is a potent antagonist of the CC chemokine receptor 4 (CCR4), a G protein-coupled receptor that binds chemokines CCL17 (TARC) and CCL22 (MDC). By binding to CCR4, C-021 blocks receptor activation and downstream signaling, preventing chemokine-induced chemotaxis of CCR4-expressing cells. The compound inhibits CCL22-induced chemotaxis and [35S]GTPγS binding in mouse B300-19 cells with IC50 values of 18.0 nM and 39.0 nM, respectively. For human CCR4 receptors, C-021 inhibits functional chemotaxis with an IC50 of 140 nM. The compound significantly reduces microglia activation and phosphorylation of ERK1/2.
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| ln Vitro |
C-021 (compound 1b) was evaluated for its in vitro oxidative hindrance stability by determining its apparent clearance values (CLint) by drug consumption rate measurements in human liver microsomes (HML). The CLint value of C-021 is 17,377 mL/hour/kg [1].
C-021 is a potent CCR4 antagonist that significantly reduces microglia activation and phosphorylation of ERK1/2. It inhibits functional chemotaxis in humans and mice with IC50s of 140 nM and 39 nM, respectively. The compound inhibits CCL22-induced chemotaxis and [35S]GTPγS binding in mouse B300-19 cells with IC50 values of 18.0 nM and 39.0 nM, respectively. For human CCR4 receptors, it demonstrates potent antagonist activity. |
| ln Vivo |
The efficacy of C-021 (compound 1b) is preliminary as a subcutaneous medication in an oxazolone-induced contact hypersensitivity assay in mice, an established model of acute skin toxicity. However, when dose C-C-021 (1 mg/kg; i.p.; daily; for 3 days) was duplicated in acute hepatic mice, small cell apoptosis was seen [2]. At 021, virtually little inhibition was detected [1].
C-021 alleviates AOM-induced cytokine upregulation in azoxymethane (AOM)-treated mice. As a CCR4 antagonist, it modulates immune cell trafficking and may reduce inflammation in vivo. CCR4 antagonism has been shown to affect Th2 cell migration and Treg function, with potential implications for allergic diseases, inflammatory conditions, and cancer immunotherapy. The compound's ability to reduce microglia activation suggests potential applications in neuroinflammatory conditions. |
| Enzyme Assay |
CCR4 binding and functional assays are performed using membrane preparations from cells expressing human or mouse CCR4 receptors. Radioligand binding studies utilize [125I]-labeled CCL22 or other appropriate tracers. Membranes are incubated with varying concentrations of C-021 and fixed radioligand in binding buffer for 60-120 minutes at room temperature. Non-specific binding is determined in the presence of excess unlabeled ligand. Bound radioligand is separated by rapid filtration and counted. [35S]GTPγS binding assays measure receptor activation by quantifying the binding of [35S]GTPγS to G proteins in response to CCR4 stimulation.
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| Cell Assay |
Cellular assays for CCR4 antagonism typically employ cells expressing human or mouse CCR4 receptors (e.g., B300-19 cells or other transfected cell lines). Chemotaxis assays are performed using Transwell chambers with CCR4-expressing cells in the upper chamber and CCL22 (the CCR4 ligand) in the lower chamber. Cells are pre-incubated with varying concentrations of C-021 before being added to the upper chamber. After incubation (2-4 hours), cells that have migrated to the lower chamber are counted. IC50 values for inhibition of chemotaxis are calculated. Calcium mobilization assays can also be used to measure CCR4 activation and inhibition.
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| Animal Protocol |
Animal/Disease Models: Male C57Bl/6 mice with acute liver failure (20-25 g) [2]
Doses: 1 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; continued for 3 days Experimental Results: Microglia Hyperplasia was Dramatically diminished, and the ratio of pERK1/2 to tERK1/2 was Dramatically diminished. In vivo efficacy of C-021 is typically evaluated in mouse models of inflammation or cancer. For inflammation studies, mice are treated with C-021 (typically administered intraperitoneally or orally) and challenged with inflammatory stimuli. Cytokine levels in tissues or serum are measured by ELISA. For cancer studies, the compound may be evaluated in tumor models to assess the effect of CCR4 blockade on tumor growth and immune cell infiltration. The compound's effect on microglia activation can be studied in neuroinflammation models. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for C-021 are limited as it is a research compound. The compound has molecular formula C27H41N5O2 and molecular weight 467.65. It is a small molecule with reasonable membrane permeability. The compound is soluble in DMSO and other organic solvents. For in vivo studies, typical formulations may include DMSO/PEG400/saline mixtures or other suitable vehicles. Standard pharmacokinetic studies would be required for any therapeutic development.
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| Toxicity/Toxicokinetics |
Toxicological data for C-021 are limited as it is a research compound. As a CCR4 antagonist, potential toxicities may be related to immune modulation, including effects on T cell trafficking and function. The compound should be handled with appropriate laboratory safety precautions. In preclinical studies, C-021 has been evaluated in mouse models with acceptable tolerability at the doses used.
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| References |
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| Additional Infomation |
C-021 is a potent CC chemokine receptor-4 (CCR4) antagonist. It is a cell-permeable di-aminoquinazoline compound that inhibits CCR4-mediated chemotaxis in human and mouse cells. The compound has anti-inflammatory activity and has been studied for its potential in treating inflammatory diseases and cancer. CCR4 is a therapeutic target for allergic diseases, inflammatory conditions, and cancer immunotherapy.
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| Molecular Formula |
2[C27H41N5O2].6[HCL].3[H2O]
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| Molecular Weight |
1208.10496
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| Exact Mass |
467.326
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| CAS # |
864289-85-0
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| Related CAS # |
C-021 dihydrochloride;1784252-84-1
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| PubChem CID |
25141190
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.312
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
602
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C2C(=C1)C(=NC(=N2)N3CCC(CC3)N4CCCCC4)NC5CCCCCC5)OC
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| InChi Key |
WYVBISCFCHREDA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H41N5O2/c1-33-24-18-22-23(19-25(24)34-2)29-27(30-26(22)28-20-10-6-3-4-7-11-20)32-16-12-21(13-17-32)31-14-8-5-9-15-31/h18-21H,3-17H2,1-2H3,(H,28,29,30)
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| Chemical Name |
N-cycloheptyl-6,7-dimethoxy-2-(4-piperidin-1-ylpiperidin-1-yl)quinazolin-4-amine
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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 : ~50 mg/mL (~106.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.71 mg/mL (1.52 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 7.1 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: ≥ 0.71 mg/mL (1.52 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 7.1 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: ≥ 0.71 mg/mL (1.52 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 | 0.8277 mL | 4.1387 mL | 8.2774 mL | |
| 5 mM | 0.1655 mL | 0.8277 mL | 1.6555 mL | |
| 10 mM | 0.0828 mL | 0.4139 mL | 0.8277 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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