CCR1 激动剂双喹啉具有强大的佐剂活性。
Potent adjuvantic activity of a CCR1-agonistic bis-quinoline.
机构信息
Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66047, United States.
出版信息
Bioorg Med Chem Lett. 2012 Jan 1;22(1):293-5. doi: 10.1016/j.bmcl.2011.11.014. Epub 2011 Nov 9.
Abstract
A bis-quinoline compound, (7-chloro-N-(4-(7-chloroquinolin-4-ylamino)butyl)quinolin-4-amine; RE-660) was found to have C-C chemokine receptor type 1 (CCR1)-agonistic properties. RE-660 displayed strong adjuvantic activity in mice when co-administered with bovine α-lactalbumin used as a model subunit protein antigen. RE-660 evoked a balanced Th1 (IgG2)/Th2 (IgG1) antibody profile, and the quality of antibodies elicited by the bis-quinoline was found to be superior to that evoked by glucopyranosyl lipid A by surface plasmon resonance experiments. No evidence of proinflammatory activity was observed in human blood ex vivo models. In preliminary acute toxicity studies, the compound was found to be of lower toxicity than chloroquine in mice, and was non-mutagenic in an Ames screen.
摘要
一种双喹啉化合物（7-氯-N-（4-（7-氯喹啉-4-基氨基）丁基）喹啉-4-胺；RE-660）被发现具有 C-C 趋化因子受体 1（CCR1）激动剂特性。当与牛α-乳白蛋白一起给药时，RE-660 作为模型亚基蛋白抗原在小鼠中显示出强烈的佐剂活性。RE-660 引起了平衡的 Th1（IgG2）/Th2（IgG1）抗体谱，并且通过表面等离子体共振实验发现，双喹啉引发的抗体质量优于葡糖基脂质 A 引发的抗体质量。在体外人体血液模型中未观察到促炎活性的证据。在初步的急性毒性研究中，该化合物在小鼠中的毒性低于氯喹，并且在艾姆斯筛选中无致突变性。
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