Potent adjuvantic activity of a CCR1-agonistic bis-quinoline

Rehman Ukani, Tyler C. Lewis, Timothy P. Day, Wenyan Wu, Subbalakshmi S. Malladi, Hemamali J. Warshakoon, Sunil A. David

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)293-295
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2012

Bibliographical note

Funding Information:
This work was supported by NIH/NIAID contract HHSN272200900033C.

Keywords

  • Adjuvants
  • Bis-quinolines
  • CCR1
  • Cytokines
  • Vaccines

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