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

doi:10.1016/j.bmcl.2011.11.014

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

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	293-295
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2011.11.014
State	Published - Jan 1 2012

Bibliographical note

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

Keywords

Adjuvants
Bis-quinolines
CCR1
Cytokines
Vaccines

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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.",

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AU - Day, Timothy P.

AU - Wu, Wenyan

AU - Malladi, Subbalakshmi S.

AU - Warshakoon, Hemamali J.

AU - David, Sunil A.

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Potent adjuvantic activity of a CCR1-agonistic bis-quinoline

Abstract

Bibliographical note

Keywords

UN SDGs

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