Pamoic Acid
(Synonyms: 帕莫酸) 目录号 : GC44553
A potent agonist of GPR35 orphan receptors
Cas No.:130-85-8
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
Pamoic acid is a potent agonist of GPR35 orphan receptors (EC50 = 79 nM in a β-arrestin recruitment assay). It induces GPR35 translocation from the plasma membrane to the cytoplasm with an EC50 value of 22 nM. Pamoic acid also increases ERK1/2 phosphorylation in a concentration-dependent manner in U20S cells expressing human GPR35a. In vivo, pamoic acid has antinociceptive effects with an ED50 value of 40.5 mg/kg in a mouse abdominal constriction model of visceral pain perception. Pamoate salts, of which pamoic acid is the main constituent, have been used in drug formulations to extend the duration of action.
| Cas No. | 130-85-8 | SDF | |
| 别名 | 帕莫酸 | ||
| Canonical SMILES | OC(C1=CC(C=CC=C2)=C2C(CC3=C(C=CC=C4)C4=CC(C(O)=O)=C3O)=C1O)=O | ||
| 分子式 | C23H16O6 | 分子量 | 388.4 |
| 溶解度 | DMSO: 0.2 mg/ml,Methanol: slightly soluble | 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 | 2.5747 mL | 12.8733 mL | 25.7467 mL |
| 5 mM | 0.5149 mL | 2.5747 mL | 5.1493 mL |
| 10 mM | 0.2575 mL | 1.2873 mL | 2.5747 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。
Pamoic Acid is an inhibitor of HMGB1·CXCL12 elicited chemotaxis and reduces inflammation in murine models of Pseudomonas aeruginosa pneumonia
Mol Med 2022 Sep 7;28(1):108.PMID:36071400DOI:10.1186/s10020-022-00535-z.
Background: High-mobility group box 1 protein (HMGB1) is an ubiquitous nuclear protein that once released in the extracellular space acts as a Damage Associated Molecular Pattern and promotes inflammation. HMGB1 is significantly elevated during Pseudomonas aeruginosa infections and has a clinical relevance in respiratory diseases such as Cystic Fibrosis (CF). Salicylates are HMGB1 inhibitors. To address pharmacological inhibition of HMGB1 with small molecules, we explored the therapeutic potential of Pamoic Acid (PAM), a salicylate with limited ability to cross epithelial barriers. Methods: PAM binding to HMGB1 and CXCL12 was tested by Nuclear Magnetic Resonance Spectroscopy using chemical shift perturbation methods, and inhibition of HMGB1·CXCL12-dependent chemotaxis was investigated by cell migration experiments. Aerosol delivery of PAM, with single or repeated administrations, was tested in murine models of acute and chronic P. aeruginosa pulmonary infection in C57Bl/6NCrlBR mice. PAM efficacy was evaluated by read-outs including weight loss, bacterial load and inflammatory response in lung and bronco-alveolar lavage fluid. Results: Our data and three-dimensional models show that PAM is a direct ligand of both HMGB1 and CXCL12. We also showed that PAM is able to interfere with heterocomplex formation and the related chemotaxis in vitro. Importantly, PAM treatment by aerosol was effective in reducing acute and chronic airway murine inflammation and damage induced by P. aeruginosa. The results indicated that PAM reduces leukocyte recruitment in the airways, in particular neutrophils, suggesting an impaired in vivo chemotaxis. This was associated with decreased myeloperoxidase and neutrophil elastase levels. Modestly increased bacterial burdens were recorded with single administration of PAM in acute infection; however, repeated administration in chronic infection did not affect bacterial burdens, indicating that the interference of PAM with the immune system has a limited risk of pulmonary exacerbation. Conclusions: This work established the efficacy of treating inflammation in chronic respiratory diseases, including bacterial infections, by topical delivery in the lung of PAM, an inhibitor of HMGB1.
Quantitative determination of Pamoic Acid in dog and rat serum by automated ion-pair solid-phase extraction and reversed-phase high-performance liquid chromatography
J Chromatogr B Biomed Sci Appl 1998 Sep 25;716(1-2):315-23.PMID:9824246DOI:10.1016/s0378-4347(98)00273-4.
Pamoic Acid is used as a counter ion to obtain long-acting pharmaceutical formulations of certain basic drugs. In order to investigate the pharmacokinetics of Pamoic Acid, a simple, sensitive and reliable method has been established for the quantitative determination of Pamoic Acid in serum from dog and rat. The method uses ion-pair solid-phase extraction followed by ion-pair reversed-phase high-performance liquid chromatograpy. The influence on recovery of the addition of different agents (tetrabutylammonium acetate, methanol, sodium hydroxide) to the serum samples prior to solid-phase extraction was studied and the analytical method was validated. The method was found to be valid for accurate, precise and selective determination of Pamoic Acid in the tested concentration range of 5-200 ng/ml serum. The overall performance of the HPLC method was found to be satisfactory for the purpose of determining concentrations of Pamoic Acid in serum samples from pharmacokinetic studies with Pamoic Acid in dogs and rats.
Structural insights on the Pamoic Acid and the 8 kDa domain of DNA polymerase beta complex: towards the design of higher-affinity inhibitors
BMC Struct Biol 2008 Apr 16;8:22.PMID:18416825DOI:10.1186/1472-6807-8-22.
Background: DNA polymerase beta (pol beta), the error-prone DNA polymerase of single-stranded DNA break repair as well as base excision repair pathways, is overexpressed in several tumors and takes part in chemotherapeutic agent resistance, like that of cisplatin, through translesion synthesis. For this reason pol beta has become a therapeutic target. Several inhibitors have been identified, but none of them presents a sufficient affinity and specificity to become a drug. The fragment-based inhibitor design allows an important improvement in affinity of small molecules. The initial and critical step for setting up the fragment-based strategy consists in the identification and structural characterization of the first fragment bound to the target. Results: We have performed docking studies of Pamoic Acid, a 9 micromolar pol beta inhibitor, and found that it binds in a single pocket at the surface of the 8 kDa domain of pol beta. However, docking studies provided five possible conformations for Pamoic Acid in this site. NMR experiments were performed on the complex to select a single conformation among the five retained. Chemical Shift Mapping data confirmed Pamoic Acid binding site found by docking while NOESY and saturation transfer experiments provided distances between pairs of protons from the Pamoic Acid and those of the 8 kDa domain that allowed the identification of the correct conformation. Conclusion: Combining NMR experiments on the complex with docking results allowed us to build a three-dimensional structural model. This model serves as the starting point for further structural studies aimed at improving the affinity of Pamoic Acid for binding to DNA polymerase beta.
Targeting of the orphan receptor GPR35 by Pamoic Acid: a potent activator of extracellular signal-regulated kinase and β-arrestin2 with antinociceptive activity
Mol Pharmacol 2010 Oct;78(4):560-8.PMID:20826425DOI:10.1124/mol.110.066746.
Known agonists of the orphan receptor GPR35 are kynurenic acid, zaprinast, 5-nitro-2-(3-phenylproplyamino) benzoic acid, and lysophosphatidic acids. Their relatively low affinities for GPR35 and prominent off-target effects at other pathways, however, diminish their utility for understanding GPR35 signaling and for identifying potential therapeutic uses of GPR35. In a screen of the Prestwick Library of drugs and drug-like compounds, we have found that Pamoic Acid is a potent GPR35 agonist. Pamoic Acid is considered by the Food and Drug Administration as an inactive compound that enables long-acting formulations of numerous drugs, such as the antihelminthics oxantel pamoate and pyrantel pamoate; the psychoactive compounds hydroxyzine pamoate (Vistaril) and imipramine pamoate (Tofranil-PM); and the peptide hormones triptorelin pamoate (Trelstar) and octreotide pamoate (OncoLar). We have found that Pamoic Acid induces a G(i/o)-linked, GPR35-mediated increase in the phosphorylation of extracellular signal-regulated kinase 1/2, recruitment of β-arrestin2 to GPR35, and internalization of GPR35. In mice, it attenuates visceral pain perception, indicating an antinociceptive effect, possibly through GPR35 receptors. We have also identified in collaboration with the Sanford-Burnham Institute Molecular Libraries Probe Production Center new classes of GPR35 antagonist compounds, including the nanomolar potency antagonist methyl-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate (CID2745687). Pamoic Acid and potent antagonists such as CID2745687 present novel opportunities for expanding the chemical space of GPR35, elucidating GPR35 pharmacology, and stimulating GPR35-associated drug development. Our results indicate that the unexpected biological functions of Pamoic Acid may yield potential new uses for a common drug constituent.
Photophysical and Fluorescence Nitroaromatic Sensing Properties of Methylated Derivative of a Pamoic Acid Ester
J Fluoresc 2023 Jan;33(1):77-90.PMID:36251202DOI:10.1007/s10895-022-03038-6.
Rapid and selective detection of nitroaromatic explosives is very important for public safety, life, and environmental health. Current instrumental techniques suffer from high cost and poor site used. In order to investigate fluorescence sensing of nitroaromatics, we prepare a new small fluorescence probe derived from Pamoic Acid. This study covers the synthesis of Pamoic Acid based [diisopropyl 4,4'-methylenebis(3-methoxy-2-naphthoate)] (2) material and characterization of its structure. The methylation of Pamoic Acid ester, which we have successfully synthesized in our previous studies, was carried out in this study. Determination of the photophysical and fluorescent nitroaromatic detection properties of the compound forms the basis of the study. Structural characterization of the synthesized compound [diisopropyl 4,4'-methylenebis(3-methoxy-2-naphthoate)] (2) was characterized using spectroscopic methods. In addition, Molecular structure of the synthesized compound was determined by single crystal X-ray diffraction studies. In the final step, compounds [diisopropyl 4,4'-methylenebis(3-hydroxy-2-naphthoate)] (1) and [diisopropyl 4,4'-methylenebis(3-methoxy-2-naphthoate)] (2) were tested as fluorescent probes for the detection of some nitroaromatic explosives. It is seen that Nitrobenzene provides the best quenching effect on the compound [diisopropyl 4,4'-methylenebis(3-hydroxy-2-naphthoate)] (1) containing the -OH group, with lowest the limit of detection (LOD) value. It was observed that Picric acid provided the best quenching effect with lowest the limit of detection (LOD) value in the compound [diisopropyl 4,4'-methylenebis(3-methoxy-2-naphthoate)] (2) obtained by methylation of the -OH group in the compound [diisopropyl 4,4'-methylenebis(3-hydroxy-2-naphthoate)] (1).