Nicotinamide N -Oxides as CXCR2 antagonists

Cutshall, Neil S.; Ursino, Rocky; Kucera, Kristin A.; Latham, John; Ihle, Nathan C.

doi:10.1016/s0960-894x(01)00326-2

Cited by 33 publications

(22 citation statements)

References 11 publications

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“…As a consequence, different classes of small CXCR2 antagonists have been developed, including diarylureas, thiazolo-and imidazolylpyrimidines, quinoxalines, nicotinamide N-oxides, indole carboxylic acids, and arylpropionic acids (Cutshall et al, 2001;Barth et al, 2002;Li et al, 2003;Widdowson et al, 2004;Allegretti et al, 2005;Baxter et al, 2006;Ho et al, 2006). In this study, we selected seven different CXCR2 antagonists from the diarylurea, imidazolylpyrimidine, and thiazolopyrimidine class and studied their mechanisms of action at human CXCR2.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in CXCR2 knockout mice or wild-type mice treated with a CXCR2 antagonist or neutralizing antibody, lung tissue damage and ulcerative colitis are reduced, suggesting that CXCR2 is an important drug target (Buanne et al, 2007). In view of this therapeutic potential, different classes of small CXCR2 antagonist have been developed, including diarylureas (Widdowson et al, 2004), thiazolo-and imidazolylpyrimidines (Baxter et al, 2006;Ho et al, 2006), quinoxalines (Li et al, 2003), nicotinamide N-oxides (Cutshall et al, 2001), indole carboxylic acids (Barth et al, 2002), and arylpropionic acids (Allegretti et al, 2005). So far, most literature describes in vitro data of the different CXCR2 antagonist classes.…”

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confidence: 99%

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Nonpeptidergic Allosteric Antagonists Differentially Bind to the CXCR2 Chemokine Receptor

Kruijf¹,

Heteren²,

Lim³

et al. 2009

J Pharmacol Exp Ther

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The chemokine receptor CXCR2 is involved in different inflammatory diseases, like chronic obstructive pulmonary disease, psoriasis, rheumatoid arthritis, and ulcerative colitis; therefore, it is considered an attractive drug target. Different classes of small CXCR2 antagonists have been developed. In this study, we selected seven CXCR2 antagonists from the diarylurea, imidazolylpyrimide, and thiazolopyrimidine class and studied their mechanisms of action at human CXCR2. All compounds are able to displace 125

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Nonpeptidergic Allosteric Antagonists Differentially Bind to the CXCR2 Chemokine Receptor

Kruijf¹,

Heteren²,

Lim³

et al. 2009

J Pharmacol Exp Ther

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“…The non-peptide CXCR2 antagonists have diverse structures, including nicotinamide N-oxide, triazolethiol or diphenylurea (Baxter et al, 2003;Cutshall et al, 2001;White et al, 1998). The CXCR2 antagonist used in this study, SB 455821, belongs to the diphenylurea group.…”

Section: Article In Pressmentioning

confidence: 99%

A synthetic, non-peptide CXCR2 antagonist blocks MIP-2-induced neutrophil migration in mice

Matzer¹,

Zombou²,

Sarau³

et al. 2004

Immunobiology

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“…Section 12.5.1) indicated that the imidazolyl pyrimidines and diaryl ureas as well as thiazolopyrimidines bind to distinct binding sites [126]. Researchers at Celltech identified a novel series of nicotinamide N-oxides as CXCR2 antagonist [127]. For instance, 6-chloro derivatives 40 was shown to inhibit CXCR2 binding ([ 125 I]-CXCL8 IC 50 1.0 mM) and was able to moderate CXCL1-driven neutrophil chemotaxis (IC 50 1.1 mM).…”

Section: -Imidazolyl Pyrimidinesmentioning

confidence: 99%

Low Molecular Weight CXCR2 Antagonists as Promising Therapeutics

Mihara¹,

Wijkmans²

2010

Methods and Principles in Medicinal Chemistry

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The chemokine receptor CXCR2 recognizes endogenous chemokines that possess a N-terminal Glu-Leu-Arg (ELR) þ amino acid sequence immediately adjacent to their CXC motif. CXCR2 and the closely related receptor CXCR1 are expressed on the cellular surface of leukocytes, notably neutrophils, endothelial cells and a range of other cell types throughout the human body. It has been firmly established now that CXCR2 plays a critical role in the development of numerous inflammatory disorders, wound healing and tumor progression [1-5]. As classically defined for chemokine receptors, CXCR2 mediates cell migration but has also been recognized as a key angiogenic factor [6,7]. These multifunctional roles have drawn increased attention to CXCR2 as a potentially successful drug target for therapeutic intervention in a range of diseases. The first half of this chapter summarizes the biological role of CXCR2 and its involvement, particularly in inflammatory disorders, in order to illuminate the potential clinical impact and relevance of CXCR2 blocking strategies. A review of all currently known low molecular weight (LMW) CXCR2 antagonists is addressed in the second half of this chapter. CXCR2 Ligands and Signal TransductionCXCR2, which shows 78% overall amino acid identity with CXCR1, was first cloned in 1991 out of human promyelocytic leukemia HL60 cells [8]. Subsequent research demonstrated that CXCR2 is the cognate receptor for at least seven structurally related (ELR) þ chemokines, which are growth-related protein (Gro)-a, -b and -c (CXCL1-CXCL3), epithelium-derived neutrophil attractant-78 (ENA-78; CXCL5), granulocyte chemotactic protein-2 (GCP-2; CXCL6), neutrophil-activating peptide-2 (NAP-2; CXCL7) and interleukin-8 (IL-8; CXCL8) [9, 10]. In contrast,

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Nicotinamide N -Oxides as CXCR2 antagonists

Cited by 33 publications

References 11 publications

Nonpeptidergic Allosteric Antagonists Differentially Bind to the CXCR2 Chemokine Receptor

Nonpeptidergic Allosteric Antagonists Differentially Bind to the CXCR2 Chemokine Receptor

A synthetic, non-peptide CXCR2 antagonist blocks MIP-2-induced neutrophil migration in mice

Low Molecular Weight CXCR2 Antagonists as Promising Therapeutics

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