GW791343 dihydrochloride
目录号 : GC36202
GW791343 dihydrochloride是P2X7变构调节剂，有种属特异性，对人P2X7的pIC50为6.9-7.2。
Cas No.:1019779-04-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
GW791343 dihydrochloride is a P2X7 allosteric modulator; exhibits species-specific activity and acts as a negative allosteric modulator of human P2X7 (pIC50 = 6.9 - 7.2). IC50 value: 7 (pIC50)Target: P2X7 in vitro: In cells expressing human P2X7 receptors, GW 791343 inhibits agonist-stimulated ethidium accumulation in both sucrose and NaCl buffer. In NaCl buffer, GW 791343 reduces the maximal response to both ATP and BzATP, but there is little effect on agonist potency except for a decrease in the presence of 300-1000 nM GW 791343. GW 791343 also reduces maximal responses to ATP and BzATP in sucrose buffer, although this effect is more marked when using ATP as agonist. In sucrose buffer, GW 791343 produces a slight decrease in ATP potency at 300 nM. GW 791343 decreases BzATP potency at concentrations of 300 nM to 10 μM. A more marked increase in agonist effect is observed when using ATP as agonist in NaCl buffer with GW791343 increasing the pEC50 and maximal response to ATP at concentrations of 10 and 30 μM. In sucrose buffer, GW791343 also increases responses when using ATP as agonist [1]. GW791343 inhibits responses at the human-rat chimeric receptor in both sucrose and NaCl buffer. GW791343 increases responses to BzATP at the F95L mutant receptor [2]. GW791343 is a non-competitive antagonist and negative allosteric modulator at the human P2X7 receptor; however, GW 791343 also acts as a positive allosteric modulator at the rat P2X7 receptor [3]. At the dog P2X7 receptor, GW 791343 is an antagonist with similar potency to that determined at the human receptor [4].
[1]. Michel AD, et al. Identification of regions of the P2X(7) receptor that contribute to human and rat species differences in antagonist effects. Br J Pharmacol, 2008, 155(5), 738-751. [2]. Felix RA, et al. Development of a comprehensive set of P2 receptor pharmacological research compounds. Purinergic Signal, 2012, 8(Suppl 1), 101-112. [3]. Roman S, et al. Cloning and pharmacological characterization of the dog P2X7 receptor. Br J Pharmacol, 2009, 158(6), 1513-1526. [4]. Michel AD, et al. Negative and positive allosteric modulators of the P2X(7) receptor. Br J Pharmacol, 2008, 153(4), 737-750.
| Cas No. | 1019779-04-4 | SDF | |
| Canonical SMILES | O=C(NC1=CC(CN2CCNCC2)=CC=C1C)CNC3=CC=C(F)C(F)=C3.[H]Cl.[H]Cl | ||
| 分子式 | C20H26Cl2F2N4O | 分子量 | 447.35 |
| 溶解度 | Water: 100 mg/mL (223.54 mM); DMSO: 20 mg/mL (44.71 mM) | 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。 |
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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 | 2.2354 mL | 11.1769 mL | 22.3539 mL |
| 5 mM | 0.4471 mL | 2.2354 mL | 4.4708 mL |
| 10 mM | 0.2235 mL | 1.1177 mL | 2.2354 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。
Negative and positive allosteric modulators of the P2X(7) receptor
Br J Pharmacol 2008 Feb;153(4):737-50.PMID:18071294DOI:10.1038/sj.bjp.0707625.
Background and purpose: Antagonist effects at the P2X(7) receptor are complex with many behaving in a non-competitive manner. In this study, the effects of N-[2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2-tricyclo[3.3.1.1(3,7)]dec-1-ylacetamide (compound-17) and N (2)-(3,4-difluorophenyl)-N (1)-[2-methyl-5-(1-piperazinylmethyl)phenyl]glycinamide dihydrochloride (GW791343) on P2X(7) receptors were examined and their mechanism of action explored. Experimental approach: Antagonist effects were studied by measuring agonist-stimulated ethidium accumulation in cells expressing human or rat recombinant P2X(7) receptors and in radioligand binding studies. Key results: Compound-17 and GW791343 were non-competitive inhibitors of human P2X(7) receptors. Receptor protection studies using decavanadate and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) showed that neither compound-17 nor GW791343 competitively interacted at the ATP binding site and so were probably negative allosteric modulators of the P2X(7) receptor. GW791343 prevented the slowly reversible blockade of the human P2X(7) receptor produced by compound-17 and inhibited [(3)H]-compound-17 binding to the P2X(7) receptor suggesting they may bind to similar or interacting sites. At rat P2X(7) receptors, compound-17 was a negative allosteric modulator but the predominant effect of GW791343 was to increase agonist responses. Antagonist interaction and radioligand binding studies revealed that GW791343 did not interact at the ATP binding site but did interact with the compound-17 binding site suggesting that GW791343 is a positive allosteric modulator of the rat P2X(7) receptor. Conclusions: Compound-17 was a negative allosteric modulator of human and rat P2X(7) receptors. GW791343 was a negative allosteric modulator of the human P2X(7) receptor but at the rat P2X(7) receptor its predominant effect was positive allosteric modulation. These compounds should provide valuable tools for mechanistic studies on P2X(7) receptors.
Identification of regions of the P2X(7) receptor that contribute to human and rat species differences in antagonist effects
Br J Pharmacol 2008 Nov;155(5):738-51.PMID:18660826DOI:10.1038/bjp.2008.306.
Background and purpose: Several P2X(7) receptor antagonists are allosteric inhibitors and exhibit species difference in potency. Furthermore, N(2)-(3,4-difluorophenyl)-N(1)-(2-methyl-5-(1-piperazinylmethyl)phenyl)glycinamide dihydrochloride (GW791343) exhibits negative allosteric effects at the human P2X(7) receptor but is a positive allosteric modulator of the rat P2X(7) receptor. In this study we have identified several regions of the P2X(7) receptor that contribute to the species differences in antagonist effects. Experimental approach: Chimeric human-rat P2X(7) receptors were constructed with regions of the rat receptor being inserted into the human receptor. Antagonist effects at these receptors were measured in ethidium accumulation and radioligand binding studies. Key results: Exchanging regions of the P2X(7) receptor close to transmembrane domain 1 modified the effects of KN62, 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) and GW791343. Further studies, in which single amino acids were exchanged, identified amino acid 95 as being primarily responsible for the differential allosteric effects of GW791343 and, to varying degrees, the species differences in potency of SB203580 and KN62. The species selectivity of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid was affected by multiple regions of the receptor, with potency being particularly affected by the amino acid 126 but not by amino acid 95. A further region of the rat receptor (amino acids 154-183) was identified that, when inserted into the corresponding position in the human receptor, increased ATP potency 10-fold. Conclusions: This study has identified several key residues responsible for the species differences in antagonist effects at the P2X(7) receptor and also identified a further region of the P2X(7) receptor that can significantly affect agonist potency at the P2X(7) receptor.