Potent Adjuvantic Activity of a CCR1-agonistic Bis-Quinoline
| Autor: | Rehman Ukani, Wenyan Wu, Sunil A. David, Hemamali J. Warshakoon, Subbalakshmi S. Malladi, Timothy P. Day, Tyler C. Lewis |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
CCR1
Transcriptional Activation Protein subunit Clinical Biochemistry Receptors CCR1 Pharmaceutical Science Pharmacology Biochemistry Article Proinflammatory cytokine chemistry.chemical_compound Chemokine receptor Mice Structure-Activity Relationship Drug Discovery Animals Humans Molecular Biology Inflammation Dose-Response Relationship Drug Chemistry Mutagenicity Tests Organic Chemistry Quinoline Chloroquine Lipids Acute toxicity Models Chemical Immunoglobulin G Toxicity Lactalbumin Quinolines Molecular Medicine Cattle Ex vivo |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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