title: Potent adjuvantic activity of a CCR1-agonistic bis-quinoline.
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.
authors: Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66047, United States.
authors: Rehman
authors: R
authors: Ukani
authors: Tyler C
authors: TC
authors: Lewis
authors: Timothy P
authors: TP
authors: Day
authors: Wenyan
authors: W
authors: Wu
authors: Subbalakshmi S
authors: SS
authors: Malladi
authors: Hemamali J
authors: HJ
authors: Warshakoon
authors: Sunil A
authors: SA
authors: David
mesh_terms: D000818:Animals; D002417:Cattle; D002738:Chloroquine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation; D007768:Lactalbumin / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008956:Models, Chemical; D009152:Mutagenicity Tests; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D054389:Receptors, CCR1 / Q000819:agonists*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
chemical_list: C573779:7-chloro-N-(4-(7-chloroquinolin-4-ylamino)butyl)quinolin-4-amine; C515300:CCR1 protein, human; D007074:Immunoglobulin G; D008055:Lipids; D011804:Quinolines; D054389:Receptors, CCR1; D002738:Chloroquine; D007768:Lactalbumin