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| 5mg |
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| Targets |
GPR52 antagonist-1 targets GPR52, a G protein-coupled receptor. GPR52 is an orphan GPCR that has been implicated in the regulation of striatal function and is a potential therapeutic target for Huntington's disease. By antagonizing GPR52, the compound reduces mutant huntingtin protein levels and promotes the survival of primary striatal neurons in mice. The compound has an IC50 of 0.63 μM for GPR52.
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| ln Vitro |
In vitro, GPR52 antagonist-1 inhibits GPR52 with an IC50 of 0.63 μM. It reduces mutant huntingtin (mHTT) protein levels in cellular models. The compound promotes the survival of mouse primary striatal neurons. These effects are mediated through GPR52 antagonism, which modulates signaling pathways involved in neuronal survival and protein homeostasis. However, detailed in vitro activity data against other targets are not extensively reported.
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| ln Vivo |
HdhQ140 mice that receive GPR52 antagonist-1 (compound 43) (5 mg/kg; i.p.; once daily for 4 weeks) exhibit a reduction in mHTT levels as well as a rescue of HD-related phenotypes [1].
In vivo, GPR52 antagonist-1 (5 mg/kg; i.p.; once daily for 4 weeks) reduces mHTT levels and rescues HD-related phenotypes in HdhQ140 mice (a mouse model of Huntington's disease). This demonstrates the compound's potential for treating Huntington's disease by reducing the levels of the toxic mutant huntingtin protein. The compound is administered intraperitoneally and shows efficacy in a chronic dosing regimen. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for GPR52 antagonist-1 typically involve radioligand binding or functional assays using cells expressing GPR52. For binding assays, membrane preparations from GPR52-expressing cells are incubated with a radiolabeled GPR52 ligand and various concentrations of the compound (0.001-100 μM) at room temperature for 1-2 hours. Bound radioactivity is measured by filtration and scintillation counting. For functional assays, cAMP accumulation or β-arrestin recruitment is measured in GPR52-expressing cells stimulated with a GPR52 agonist. The IC50 is determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for GPR52 antagonist-1 use primary striatal neurons from mice or cell lines expressing GPR52. Cells are cultured in appropriate media and treated with various concentrations of the compound (0.001-10 μM) for 24-72 hours. Mutant huntingtin protein levels are quantified by Western blotting or ELISA. Neuronal survival is assessed by MTT or CellTiter-Glo assays. Apoptosis is assessed by caspase-3/7 activity. GPR52-mediated signaling (e.g., cAMP levels) is measured to confirm target engagement.
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| Animal Protocol |
In vivo animal studies with GPR52 antagonist-1 use HdhQ140 mice, a transgenic mouse model of Huntington's disease. Mice are administered the compound intraperitoneally at 5 mg/kg once daily for 4 weeks. At study termination, brain tissue is harvested for analysis of mHTT levels by Western blotting or ELISA. HD-related phenotypes such as motor function and body weight are assessed. Striatal neuron survival is evaluated by histology.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GPR52 antagonist-1: The compound is soluble in DMSO at ~250 mg/mL (~1031.61 mM). It has a molecular weight of 242.34 and a LogP of 4.3, indicating high lipophilicity. Specific PK parameters such as oral bioavailability, half-life, and tissue distribution are not extensively reported. The compound is administered intraperitoneally in animal studies. It is expected to cross the blood-brain barrier due to its lipophilic nature.
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| Toxicity/Toxicokinetics |
The toxicity profile of GPR52 antagonist-1 is not extensively reported. As a GPR52 antagonist, potential toxicities may include effects on striatal function and other GPR52-expressing tissues. The compound is for research use only and not for human therapeutic use. Standard toxicity studies would include acute and subchronic toxicity in rodents, with monitoring of body weight, clinical signs, and histopathology. No specific genotoxicity or cardiotoxicity data are reported.
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| References |
[1]. Wang C, et al. GPR52 Antagonist Reduces Huntingtin Levels and Ameliorates Huntington's Disease-Related Phenotypes. J Med Chem. 2021 Jan 28;64(2):941-957.
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| Additional Infomation |
GPR52 antagonist-1 (CAS 1239987-91-7, Compound 43) is a selective GPR52 antagonist with an IC50 of 0.63 μM. It has a molecular formula of C15H14OS and a molecular weight of 242.34. The compound reduces mutant huntingtin protein levels and promotes survival of primary striatal neurons in mice, with potential applications in Huntington's disease research. It is available for research purposes only.
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| Molecular Formula |
C15H14OS
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| Molecular Weight |
242.336062908173
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| Exact Mass |
242.076
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| CAS # |
1239987-91-7
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| PubChem CID |
156588927
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| Appearance |
White to light yellow solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
17
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| Complexity |
266
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)CC/C=C/C(=O)C2=CC=CS2
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| InChi Key |
XUIAIACHIPOOHR-BJMVGYQFSA-N
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| InChi Code |
InChI=1S/C15H14OS/c16-14(15-11-6-12-17-15)10-5-4-9-13-7-2-1-3-8-13/h1-3,5-8,10-12H,4,9H2/b10-5+
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| Chemical Name |
(E)-5-phenyl-1-thiophen-2-ylpent-2-en-1-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~1031.61 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.58 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (8.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1264 mL | 20.6322 mL | 41.2643 mL | |
| 5 mM | 0.8253 mL | 4.1264 mL | 8.2529 mL | |
| 10 mM | 0.4126 mL | 2.0632 mL | 4.1264 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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