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Potent Adjuvantic Activity of a CCR1-agonistic Bis-Quinoline
Ukani, Rehman Lewis, Tyler C. Day, Timothy P. Wu, Wenyan Malladi, Subbalakshmi S. Warshakoon, Hemamali J. David, Sunil A.
Ukani, Rehman
Lewis, Tyler C.
Day, Timothy P.
Wu, Wenyan
Malladi, Subbalakshmi S.
Warshakoon, Hemamali J.
David, Sunil A.
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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.
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Date
2012-01-01
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Elsevier
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Keywords
Vaccines, Adjuvants, Bis-quinolines, CCR1, Cytokines
Citation
Ukani, R., Lewis, T. C., Day, T. P., Wu, W., Malladi, S. S., Warshakoon, H. J., & David, S. A. (2012). Potent Adjuvantic Activity of a CCR1-agonistic Bis-Quinoline. Bioorganic & Medicinal Chemistry Letters, 22(1), 293–295. http://doi.org/10.1016/j.bmcl.2011.11.014