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INCB3344
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
INCB3344图片
CAS NO:1262238-11-8
规格:98%
分子量:577.24
包装与价格:
包装价格(元)
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍
CCR2 chemokine receptor antagonist
CAS:1262238-11-8
分子式:C29H34F3N3O6
分子量:577.24
纯度:98%
存储:Store at -20°C

Background:

INCB3344 is a novel potent and selective antagonist of CCR2 receptor, which possesses an IC 50 of 10 nM for CCL2. [1]



CCR2 is a chemokine receptor mainly expressed on monocytes which acts as the key receptor in mediating their tissue influx in the context of immune-based inflammation. CCR2 is a G protein-coupled receptor (GPCR), whose ligands include the chemokines MCP family, including CCL2, CCL7, CCL8. These ligands bind CCR2 receptor with high affinity and elicit a chemotactic signal which leads to directed migration of the receptor-bearing cells. CCL2 has been shown to be relevant in high concentrations in various inflammatory lesions, implicating this chemokine as a physiologically important chemotactic signal for monocytes. [1]


Characterization of the pharmacological activity of INCB3344 was first evaluated by testing its ability to inhibit CCL2 binding to CCR2 in a whole cell binding assay using a murine monocyte cell line, WEHI-274.1 and 125I-labeled mCCL2 as a tracer. The binding IC 50 of INCB3344 in this assay was determined to be 10±5 nM, and inhibition greater than 90% binding was observed at a concentration of 90nM . The chemotaxis inhibitory activity of different concentrations of INCB3344 was evaluated using 30nM mCCL2 as the agonist. The result showed a similar potency to the binding assay. Selectivity of INCB3344 was evaluated against a panel of GPCRs including several human chemokine receptors using radioligand binding assays. Results from these studies demonstrate at least 100-fold selectivity of INCB3344 against all of the receptors tested. [1]


INCB3344 treatment results in a dose-dependent inhibition of macrophage influx in a mouse delayed-type hypersensitivity model. The histopathological analysis of tissues from the delayed-type hypersensitivity model illustrates that inhibitory activity of CCR2 leads to a substantial reduction in tissue inflammation. [1]


Reference:
[1].  Brodmerkel C M, Huber R, Covington M, et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344[J]. The Journal of Immunology, 2005, 175(8): 5370-5378.