Home>>Signaling Pathways>> GPCR/G protein>> CCR>>CCR1 antagonist 1

CCR1 antagonist 1 Sale

目录号 : GC31996

CCR1 拮抗剂 1 是 CCR1 的拮抗剂,具有抗炎活性。

CCR1 antagonist 1 Chemical Structure

Cas No.:1010073-75-2

规格 价格 库存 购买数量
1mg
¥11,424.00
现货
5mg
¥22,848.00
现货
10mg
¥38,824.00
现货
20mg
¥68,544.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

产品描述

CCR1 antagonist 1 is an antagonist of CCR1, with anti-inflammatory activity.

CCR1 antagonist 1 shows potent activities in the chemotaxis assay, with IC50 < 100 nM[1].

In vivo, CCR1 antagonist 1 has in vivo anti-inflammatory activity and has superior pharmacokinetic properties[1].

[1]. Compounds for the treatment of osteoporosis and cancers. US 20100113472 A1

Chemical Properties

Cas No. 1010073-75-2 SDF
Canonical SMILES COC1=CC(N2CCN(C(CN3N=C(C4=NC=CN4)C5=CC=CN=C53)=O)CC2)=CC=C1Cl
分子式 C22H22ClN7O2 分子量 451.91
溶解度 Soluble in DMSO 储存条件 Store at -20°C
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 2.2128 mL 11.0641 mL 22.1283 mL
5 mM 0.4426 mL 2.2128 mL 4.4257 mL
10 mM 0.2213 mL 1.1064 mL 2.2128 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置

Research Update

CCL3 Signaling in the Tumor Microenvironment

Within the tumor microenvironment, chemokines play a key role in immune cell trafficking regulation and immune landscape formulation. CCL3 or macrophage inflammatory protein-1α (MIP-1α), an important chemokine implicated in both immune surveillance and tolerance, has emerged as a prognostic biomarker in both solid and hematological malignancies. CCL3 exerts both antitumor and pro-tumor behavior which is context dependent highlighting the complexity of the underlying interrelated signaling cascades. Current CCL3-directed therapeutic approaches are investigational and further optimization is required to increase efficacy and minimize adverse events.

Small molecule antagonist of C-C chemokine receptor 1 (CCR1) reduces disc inflammation in the rabbit model

Background context: Targeting chemokines or chemokine receptors is a promising treatment strategy for diseases with chronic inflammation such as rheumatoid arthritis and discogenic pain. Identifying specific molecules and determining their effectiveness in animal models are the first steps in developing these treatments. Macrophage markers have been detected in the intervertebral disc tissues of patients with disc degenerative disease and discogenic pain and in different animal models. Macrophage recruitment into the disc may play a role in initiation of inflammation and if unresolved may lead to chronic inflammation and subsequent back pain.
Purpose: The objectives of these studies are to (1) identify chemokine receptor antagonists that can block macrophage migration induced by disc cells in vitro and (2) determine if intradiscal treatment with these antagonists can reduce disc inflammation and degeneration in vivo.
Study design: In vitro migration assays were used to test effectiveness of chemokine receptor antagonists to block macrophage migration induced by disc cells. The rabbit annular puncture model was used to test for anti-inflammatory and regenerative effects of chemokine receptor antagonist treatment in vivo.
Methods: In vitro - THP-1 human monocytic cell line and freshly isolated rabbit primary splenocytes were assayed for migration using 3 ?m Corning Transwell inserts with conditioned media of interleukin (IL)-1β treated human or rabbit disc cells. Inhibition of macrophage migration was evaluated using different concentrations of small molecule antagonists of C-C chemokine receptor (CCR)1 and CCR2. In vivo - New Zealand White rabbits (n=40) underwent disc puncture and intradiscal treatment with saline, CCR1 or CCR2 antagonists within the same procedure. X-ray and magnetic resonance (MR) images and serum samples were taken for disc height, MRI grade and IL-8 serum level analyses. Intervertebral discs were isolated for RNA analysis of inflammatory and disc phenotypic markers and for immunohistochemical analysis of macrophage marker, RAM11. The outcome measures were compared between the three treatment groups. These studies were funded by a research grant from AO Foundation, Switzerland (Project no S-14-86A; 120000 CHF). CCR1 and CCR2 antagonists were kindly provided by ChemoCentryx (Mountain View, CA).
Results: In vitro migration assays showed that THP-1 migration induced by disc cells was blocked by CCR2 antagonist more effectively than CCR1 antagonist, while rabbit splenocyte migration was inhibited by CCR1 antagonist and not the other. In the rabbit annular puncture model, rabbit discs treated with CCR1 antagonist had significantly better MRI grades than those treated with CCR2 antagonist at 6 weeks post-treatment. Gene expression studies demonstrate that discs treated with CCR1 or CCR2 antagonists expressed less inflammatory markers than saline-treated discs at 3 weeks post-treatment. Although CCR2 antagonist treatment did not reduce inflammatory marker expression at 6 weeks, discs treated with CCR1 antagonist expressed less inflammatory markers and also a higher ratio of collagen type 2 to collagen type 1 genes indicating favorable disc matrix production. There were no significant differences between all three treatment groups in regards to disc height indexes, IL-8 serum levels or macrophage marker detection.
Conclusions: These studies have identified that small molecule antagonists against CCR2 and CCR1 were respectively effective in blocking THP-1 and rabbit splenocyte migration induced by disc cells in vitro. Further, both CCR2 and CCR1 antagonist intradiscal treatments were effective in reducing disc inflammation at an early time point of 3 weeks. Lastly, only CCR1 antagonist demonstrated anti-inflammatory effects and better MRI grades at 6 weeks.
Clinical significance: Our preclinical studies demonstrate that CCR1 and CCR2 antagonist delivery through intradiscal injection is sufficient to reduce disc inflammation at early time points, whereas CCR1 antagonists had longer term anti-inflammatory effects. Clinical studies have found that CCR1 antagonist was safe, tolerable and clinically active in reducing inflammation in rheumatoid arthritis patients. These studies suggest that CCR1 antagonist may be a promising biological treatment to reduce disc inflammation that translates to back pain relief.

Macrophage inflammatory protein-1

Macrophage inflammatory protein (MIP)-1alpha was identified 15 years ago as the first of now four members of the MIP-1 CC chemokine subfamily. These proteins termed CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CCL9/10 (MIP-1delta), and CCL15 (MIP-1gamma) according to the revised nomenclature for chemokines are produced by many cells, particularly macrophages, dendritic cells, and lymphocytes. MIP-1 proteins, which act via G-protein-coupled cell surface receptors (CCR1, 3, 5), e.g. expressed by lymphocytes and monocytes/macrophages (MPhi), are best known for their chemotactic and proinflammatory effects but can also promote homoeostasis. The encouraging results of preclinical studies in murine models of inflammation, i.e. asthma, arthritis, or multiple sclerosis, have led to the development of potent CCR3 and 5 antagonists, some of which are currently being tested in first clinical trials.

Eosinophil-derived chemokine (hCCL15/23, mCCL6) interacts with CCR1 to promote eosinophilic airway inflammation

Eosinophils are terminally differentiated cells derived from hematopoietic stem cells (HSCs) in the bone marrow. Several studies have confirmed the effective roles of eosinophils in asthmatic airway pathogenesis. However, their regulatory functions have not been well elucidated. Here, increased C-C chemokine ligand 6 (CCL6) in asthmatic mice and the human orthologs CCL15 and CCL23 that are highly expressed in asthma patients are described, which are mainly derived from eosinophils. Using Ccl6 knockout mice, further studies revealed CCL6-dependent allergic airway inflammation and committed eosinophilia in the bone marrow following ovalbumin (OVA) challenge and identified a CCL6-CCR1 regulatory axis in hematopoietic stem cells (HSCs). Eosinophil differentiation and airway inflammation were remarkably decreased by the specific CCR1 antagonist BX471. Thus, the study identifies that the CCL6-CCR1 axis is involved in the crosstalk between eosinophils and HSCs during the development of allergic airway inflammation, which also reveals a potential therapeutic strategy for targeting G protein-coupled receptors (GPCRs) for future clinical treatment of asthma.

1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists

A novel series of CCR1 antagonists based on the 1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanone scaffold was identified by screening a compound library utilizing CCR1-expressing human THP-1 cells. SAR studies led to the discovery of the highly potent and selective CCR1 antagonist 14 (CCR1 binding IC(50)=4 nM using [(125)I]-CCL3 as the chemokine ligand). Compound 14 displayed promising pharmacokinetic and toxicological profiles in preclinical species.