DFP00173
目录号 : GC38769
DFP00173 是一种有效的，选择性的 aquaporin-3 (AQP3) 抑制剂。DFP00173 抑制小鼠和人 AQP3，IC50 值为 ∼0.1-0.4 μM。DFP00173 对 AQP3 的选择性高于同源 AQP 亚型 AQP7 和 AQP9。
Cas No.:672286-03-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
DFP00173 is a potent and selective aquaporin-3 (AQP3) inhibitor. DFP00173 inhibits mouse and human AQP3 with an IC50 of ∼0.1-0.4 μM. DFP00173 is selective for AQP3 over the homologous AQP isoforms AQP7 and AQP9[1].
DFP00173 inhibits the glycerol permeability of human erythrocytes with an IC50 of ~0.2 µM[1].
[1]. Sonntag Y, et al. Identification and characterization of potent and selective aquaporin-3 and aquaporin-7 inhibitors. J Biol Chem. 2019 May 3;294(18):7377-7387.
| Cas No. | 672286-03-2 | SDF | |
| Canonical SMILES | O=C(NC1=CSC([N+]([O-])=O)=C1)NC2=C(Cl)C=CC=C2Cl | ||
| 分子式 | C11H7Cl2N3O3S | 分子量 | 332.16 |
| 溶解度 | DMSO: 125 mg/mL (376.32 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 | 3.0106 mL | 15.053 mL | 30.106 mL |
| 5 mM | 0.6021 mL | 3.0106 mL | 6.0212 mL |
| 10 mM | 0.3011 mL | 1.5053 mL | 3.0106 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。
Identification and characterization of potent and selective aquaporin-3 and aquaporin-7 inhibitors
J Biol Chem 2019 May 3;294(18):7377-7387.PMID:30862673DOI:10.1074/jbc.RA118.006083.
The aquaglyceroporins are a subfamily of aquaporins that conduct both water and glycerol. Aquaporin-3 (AQP3) has an important physiological function in renal water reabsorption, and AQP3-mediated hydrogen peroxide (H2O2) permeability can enhance cytokine signaling in several cell types. The related aquaglyceroporin AQP7 is required for dendritic cell chemokine responses and antigen uptake. Selective small-molecule inhibitors are desirable tools for investigating the biological and pathological roles of these and other AQP isoforms. Here, using a calcein fluorescence quenching assay, we screened a library of 7360 drug-like small molecules for inhibition of mouse AQP3 water permeability. Hit confirmation and expansion with commercially available substances identified the ortho-chloride-containing compound DFP00173, which inhibited mouse and human AQP3 with an IC50 of ∼0.1-0.4 μm but had low efficacy toward mouse AQP7 and AQP9. Surprisingly, inhibitor specificity testing revealed that the methylurea-linked compound Z433927330, a partial AQP3 inhibitor (IC50, ∼0.7-0.9 μm), is a potent and efficacious inhibitor of mouse AQP7 water permeability (IC50, ∼0.2 μm). Stopped-flow light scattering measurements confirmed that DFP00173 and Z433927330 inhibit AQP3 glycerol permeability in human erythrocytes. Moreover, DFP00173, Z433927330, and the previously identified AQP9 inhibitor RF03176 blocked aquaglyceroporin H2O2 permeability. Molecular docking to AQP3, AQP7, and AQP9 homology models suggested interactions between these inhibitors and aquaglyceroporins at similar binding sites. DFP00173 and Z433927330 constitute selective and potent AQP3 and AQP7 inhibitors, respectively, and contribute to a set of isoform-specific aquaglyceroporin inhibitors that will facilitate the evaluation of these AQP isoforms as drug targets.
dDAVP Downregulates the AQP3-Mediated Glycerol Transport via V1aR in Human Colon HCT8 Cells
Front Cell Dev Biol 2022 Jul 8;10:919438.PMID:35874817DOI:10.3389/fcell.2022.919438.
Vasopressin (AVP) plays a key function in controlling body water and salt balance through the activation of the vasopressin receptors V1aR and V2R. Abnormal secretion of AVP can cause the syndrome of inappropriate antidiuresis that leads to hyponatremia, which is an electrolyte disorder often observed in the elderly hospitalized and oncologic patients. Beyond kidneys, the colonic epithelium modulates water and salt homeostasis. The water channel AQP3, expressed in villus epithelial cells is implicated in water absorption across human colonic surface cells. Here, the action of dDAVP, a stable vasopressin analog, was evaluated on the AQP3 expression and function using human colon HCT8 cells as an experimental model. Confocal and Western Blotting analysis revealed that HCT8 cells express both V1aR and V2R. Long-term (72 h) treatment with dDAVP reduced glycerol uptake and cell viability. These effects were prevented by SR49059, a synthetic antagonist of V1aR, but not by tolvaptan, a specific V2R antagonist. Of note, the SR49059 action was impaired by DFP00173, a selective inhibitor of AQP3. Interestingly, compared to the normal colonic mucosa, in the colon of patients with adenocarcinoma, the expression of V1aR was significantly decreased. These findings were confirmed by gene expression analysis with RNA-Seq data. Overall, data suggest that dDAVP, through the V1aR dependent pathway, reduces AQP3 mediated glycerol uptake, a process that is reversed in adenocarcinoma, suggesting that the AVP-dependent AQP3 pathway may represent a novel target in colon diseases associated with abnormal cell growth.
Application of a HyPer-3 sensor to monitor intracellular H2O2 generation induced by phenolic acids in differentiated Caco-2 cells
Anal Biochem 2022 Dec 15;659:114934.PMID:36206845DOI:10.1016/j.ab.2022.114934.
Intestinal epithelial cells (IECs) are an important point of contact between dietary food components consumed and subsequent whole-body utilization for body maintenance and growth. Selective bioactive phenolic acids, widely present in fruits, vegetables and beverages can generate hydrogen peroxide (H2O2) and contribute to the cellular redox balance, hence influencing well-known cellular antioxidant and pro-oxidant mechanisms. Our findings have showed that increasing extracellular H2O2 resulted in associated changes in intracellular H2O2 levels in Caco-2 cells (p < 0.05) which was facilitated by activity of a family of water channel membrane proteins, termed aquaporins (AQPs). To demonstrate this, a HyPer-3 genetically encoded fluorescent H2O2 sensitive indicator was used to enable fluorescent real-time imaging of intracellular H2O2 levels as a measure of changes occurring in extracellular H2O2 in differentiated Caco-2 cells exposed to different phenolic acids. The use of confocal microscopy and flow cytometry, respectively, captured visualization and quantification of H2O2 uptake in differentiated Caco-2 cells. DFP00173, an aquaporin 3 (AQP3) inhibitor was effective at inhibiting the intracellular uptake of H2O2 and was sensitive to varied levels of H2O2 generated when different phenolic acids were added to the culture media. In summary, HyPer-3 was shown to be an effective technique to demonstrate relative capabilities of structurally different dietary phenolic acids that have potential to alter intestinal redox balance by changing intracellular H2O2, and either antioxidant or pro-oxidant activity, respectively.