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Overview
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Background
C 021 dihydrochloride is a potent antagonist of CCR4 with IC50 values of 0.039 and 0.14 μM for inhibition of chemotaxis in mouse and human, respectively [1].
CC chemokine receptor 4 (CCR4) is a G protein-coupled receptor and is a receptor for the CC chemokines, which play an important role in the development and function of the immune system.
C 021 dihydrochloride is a potent CCR4 antagonist. C 021 dihydrochloride potently inhibited functional chemotaxis in mice and human with IC50 values of 0.039 and 0.14 μM, respectively. In the GTPγS-binding assay, C 021 dihydrochloride was active with IC50 value of 0.018 μM [1].
Treatment mice with azoxymethane (AOM), which induced hepatic encephalopathy, AOM significantly increased microglia activation and the concentrations of CCL2 in the liver, serum, and cortex. C 021 dihydrochloride reduced liver damage and significantly improved the neurological outcomes. Also, C 021 dihydrochloride reduced microglia activation and phosphorylation of ERK1/2, and inhibited AOM-induced cytokine upregulation [2].[1]. Yokoyama K, Ishikawa N, Igarashi S, et al. Potent and orally bioavailable CCR4 antagonists: Synthesis and structure-activity relationship study of 2-aminoquinazolines. Bioorg Med Chem, 2009, 17(1): 64-73.
[2]. McMillin M, Frampton G, Thompson M, et al. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline. J Neuroinflammation, 2014, 11: 121.
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