AZD2423
目录号 : GC60615
AZD2423是一种有效的、选择性的、口服生物利用的、非竞争性的CCR2趋化因子受体负向变构调节剂。AZD2423对CCR2Ca2+通量的IC50为1.2nM。
Cas No.:1229603-37-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
AZD2423 is a potent, selective, orally bioavailable, and non-competitive CCR2 chemokine receptor negative allosteric modulator. AZD2423 has an IC50 of 1.2 nM for CCR2 Ca2+ flux [1][2][3].
AZD2423 inhibits MCP-1 induced calcium mobilization and chemotaxis of THP-1 cell line with an IC50 of 4 nM[1].
[1]. AZD2423. [2]. John G. Cumming. CCR2 antagonists for the treatment of neuropathic pain: The discovery and development of AZD2423. [3]. KalliomÄki J, et al. A randomized, double-blind, placebo-controlled trial of a chemokine receptor 2 (CCR2) antagonist in posttraumatic neuralgia. Pain. 2013 May;154(5):761-7.
| Cas No. | 1229603-37-5 | SDF | |
| Canonical SMILES | O=C(N1CCN(C([C@@H]2NCCN(C(C)(C)C)C2)=O)CC1)NC3=CC=C(Cl)C(F)=C3 | ||
| 分子式 | C20H29ClFN5O2 | 分子量 | 425.93 |
| 溶解度 | DMSO: 200 mg/mL (469.56 mM) | 储存条件 | 4°C, stored under nitroge |
| 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。 |
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| 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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3478 mL | 11.739 mL | 23.478 mL |
| 5 mM | 0.4696 mL | 2.3478 mL | 4.6956 mL |
| 10 mM | 0.2348 mL | 1.1739 mL | 2.3478 mL |
| 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 | 只 |
| 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 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Evaluation of a novel chemokine receptor 2 (CCR2)-antagonist in painful diabetic polyneuropathy
Scand J Pain 2013 Apr 1;4(2):77-83.PMID:29913894DOI:10.1016/j.sjpain.2012.10.003.
Background and aims Preclinical data suggest that the chemokine receptor 2 (CCR2) is involved in the pathophysiology of neuropathic pain through modulation of neuronal excitability, synaptic transmission and activation of spinal cord microglia. CCR2-antagonists have shown to be effective in preclinical models of neuropathic pain. The aim of this study was to evaluate the analgesic efficacy, safety and tolerability of a novel CCR2-antagonist, AZD2423, in patients with painful diabetic neuropathy (PDN). Methods This was a double-blind, randomized, parallel-group, multi-center study in patients with symmetric distal sensory polyneuropathy due to type 1 or 2 diabetes and duration of neuropathic pain between 3 months and 5 years. Concomitant treatment with neuropathic pain medications (e.g. anticonvulsants, tricyclic antidepressants, serotonin-noradrenaline uptake inhibitors, opioids, topical lidocaine or capsaicin) was not allowed. 134 patients with PDN were equally randomized to 28 days oral administration of 20 mg AZD2423,150 mg AZD2423, or placebo. The primary efficacy variable was the change of average pain score from 5-days baseline to the last 5 days of treatment, measured with numerical rating scale (NRS, 0-10). The secondary efficacy measures included NRS worst pain scores, patient global impression of change, pain interference on sleep and activity, and neuropathic pain symptom inventory (NPSI). Results The change of NRS average pain score was not significantly different between treatment groups (AZD2423 20mg: -1.50; AZD2423 150 mg: -1.35; placebo: -1.61). The NPSI total score and three out of five subscores (evoked pain, pressing/deep pain and paresthesia/dysesthesia) tended to be reduced more by AZD2423 150 mg than by placebo. No other secondary efficacy variables differed between treatment groups. The frequency and type of adverse events for AZD2423 were similar to placebo. The achieved plasma levels of AZD2423 in the two dose groups were in line with predictions from pharmacokinetic data previously obtained in healthy volunteers. Dose-dependent increase of plasma levels of the ligand of CCR2 (CCL2; chemokine ligand 2) and decrease of the mean levels of monocytes (-27% by AZD2423 150 mg) suggested that the administrated doses of AZD2423 interacted with the CCR2 target. Conclusion The CCR2-antagonist AZD2423 showed no analgesic efficacy in PDN based on NRS average pain scores and global and functional pain outcome measures. The NPSI data suggested possible effects on certain sensory components of pain. There were no major safety or tolerability concerns. Implications Treatment with a CCR2-antagonist does not have a clinically important analgesic effect in an overall PDN population.
A randomized, double-blind, placebo-controlled trial of a chemokine receptor 2 (CCR2) antagonist in posttraumatic neuralgia
Pain 2013 May;154(5):761-767.PMID:23523116DOI:10.1016/j.pain.2013.02.003.
We evaluated the analgesic efficacy, safety and tolerability of a novel chemokine receptor 2 (CCR2) antagonist, AZD2423, in posttraumatic neuralgia. This was a double-blind, randomized, parallel-group, multicentre study. One hundred thirty-three patients with posttraumatic neuralgia were equally randomized to 28days' oral administration of 20mg AZD2423, 150mg AZD2423 or placebo. The primary efficacy variable was the change of average pain score from 5days at baseline to the last 5days of treatment, measured by a numerical rating scale (NRS, 0-10). The secondary efficacy measures included NRS worst pain score, patient global impression of change, pain interference on sleep and activity, and Neuropathic Pain Symptom Inventory (NPSI). The change of the NRS average pain score was not significantly different between treatment groups (AZD2423 20mg -1.54; AZD2423 150mg -1.53; placebo -1.44). There were trends towards larger reduction of NPSI total score and NPSI subscores for paroxysmal pain and paresthesia/dysesthesia by AZD2423 150mg compared to placebo. No other secondary efficacy variables differed between treatment groups. The frequency and type of adverse events for AZD2423 were similar to placebo. Increased plasma levels of chemokine ligand 2 and reduced mean levels of monocytes (-30% by AZD2423 150mg) suggested that the administrated doses of AZD2423 had interacted with the CCR2 target. The CCR2 antagonist AZD2423 demonstrated no efficacy on NRS average pain scores and most of the secondary pain variables. The NPSI data suggested possible effects on certain sensory components of pain. There were no major safety or tolerability concerns.