Uses
C-021 is a potent CC chemokine receptor-4 (CCR4) antagonist. C-021 potently inhibits functional chemotaxis in human and mouse with IC50s of 140 nM and 39 nM, respectively. C-021 effectively prevents human CCL22-derived [35S]GTPγS from binding to the receptor with an IC50 of 18 nM[1].
Biological Activity
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].
in vivo
The potency of C-021 (Compound 1b) is evident after subcutaneous administration in the murine oxazolone-induced contact hypersensitivity test, a known model of acute skin inflammation. When C-021 is administered orally, however, very little inhibition is observed[1].
?
C-021 (1 mg/kg; i.p.; daily; for 3 days) significantly less microgliosis in acute liver failuremice[2].
| Animal Model: | Male C57Bl/6 mice (20-25 g) with acute liver failure[2] |
| Dosage: | 1 mg/kg |
| Administration: | i.p.; daily; for 3 days |
| Result: | Significantly less microgliosis, and significantly reduced the pERK1/2 to tERK1/2 ratio. |
References
[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.
