BAY-1797
目录号 : GC39344
A P2X4 receptor antagonist
Cas No.:2055602-83-8
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
BAY-1797 is an antagonist of the purinergic P2X4 receptor (IC50 = 0.211 ?M for the human receptor).1 It is selective for P2X4 over P2X1, P2X3, and P2X7 receptors (IC50s = >50, 8.3, and 10.6 ?M, respectively, for the human receptors), as well as a panel of G protein-coupled receptors (GPCRs), ion channels, kinases, and transporters at 10 ?M. BAY-1797 (50 mg/kg) decreases intraplantar prostaglandin E2 levels and reduces non-evoked pain-related behavior in the dynamic weight bearing test in a mouse model of inflammatory pain induced by complete Freund’s adjuvant (CFA).
1.Werner, S., Mesch, S., Hillig, R.C., et al.Discovery and characterization of the potent and selective P2X4 inhibitor N-[4-(3-chlorophenoxy)-3-sulfamoylphenyl]-2-phenylacetamide (BAY-1797) and structure-guided amelioration of Its CYP3A4 induction profileJ. Med. Chem.62(24)11194-11217(2019)
| Cas No. | 2055602-83-8 | SDF | |
| Canonical SMILES | O=C(NC1=CC=C(OC2=CC=CC(Cl)=C2)C(S(=O)(N)=O)=C1)CC3=CC=CC=C3 | ||
| 分子式 | C20H17ClN2O4S | 分子量 | 416.88 |
| 溶解度 | DMSO: 250 mg/mL (599.69 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 | 2.3988 mL | 11.9939 mL | 23.9877 mL |
| 5 mM | 0.4798 mL | 2.3988 mL | 4.7975 mL |
| 10 mM | 0.2399 mL | 1.1994 mL | 2.3988 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。
Discovery and Characterization of the Potent and Selective P2X4 Inhibitor N-[4-(3-Chlorophenoxy)-3-sulfamoylphenyl]-2-phenylacetamide (BAY-1797) and Structure-Guided Amelioration of Its CYP3A4 Induction Profile
J Med Chem 2019 Dec 26;62(24):11194-11217.PMID:31746599DOI:10.1021/acs.jmedchem.9b01304.
The P2X4 receptor is a ligand-gated ion channel that is expressed on a variety of cell types, especially those involved in inflammatory and immune processes. High-throughput screening led to a new class of P2X4 inhibitors with substantial CYP 3A4 induction in human hepatocytes. A structure-guided optimization with respect to decreased pregnane X receptor (PXR) binding was started. It was found that the introduction of larger and more polar substituents on the ether linker led to less PXR binding while maintaining the P2X4 inhibitory potency. This translated into significantly reduced CYP 3A4 induction for compounds 71 and 73. Unfortunately, the in vivo pharmacokinetic (PK) profiles of these compounds were insufficient for the desired profile in humans. However, BAY-1797 (10) was identified and characterized as a potent and selective P2X4 antagonist. This compound is suitable for in vivo studies in rodents, and the anti-inflammatory and anti-nociceptive effects of BAY-1797 were demonstrated in a mouse complete Freund's adjuvant (CFA) inflammatory pain model.
Discrepancy in interactions and conformational dynamics of pregnane X receptor (PXR) bound to an agonist and a novel competitive antagonist
Comput Struct Biotechnol J 2022 Jun 13;20:3004-3018.PMID:35782743DOI:10.1016/j.csbj.2022.06.020.
Pregnane X receptor (PXR) is a nuclear receptor with an essential role in regulating drug metabolism genes. While the mechanism of action for ligand-mediated PXR agonism is well-examined, its ligand-mediated inhibition or antagonism is poorly understood. Here we employ microsecond timescale all-atom molecular dynamics (MD) simulations to investigate how our newly identified dual kinase and PXR inhibitor, compound 100, acts as a competitive PXR antagonist and not as a full agonist. We study the PXR ligand binding domain conformational changes associated with compound 100 and compare the results to the full agonist SR12813, in presence and absence of the coactivator. Furthermore, we complement our research by experimentally disclosing the effect of eight key-residue mutations on PXR activation. Finally, simulations of P2X4 inhibitor (BAY-1797) in complex with PXR, which shares an identical structural moiety with compound 100, provide further insights to ligand-induced PXR behaviour. Our MD data suggests ligand-specific influence on conformations of different PXR-LBD regions, including α6 region, αAF-2, α1-α2', β1'-α3 and β1-β1' loop. Our results provide important insights on conformational behaviour of PXR and offers guidance how to alleviate PXR agonism or to promote PXR antagonism.