| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
GPR52 (orphan G protein-coupled receptor). Gpr52 antagonist E7 acts as an intracellular covalent ligand of orphan receptor GPR52. The compound binds covalently to GPR52 through an allosteric mechanism distinct from the agonist-binding pocket.
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| ln Vitro |
Gpr52 antagonist E7 reduces mutant HTT levels in cellular models. It rescues Huntington's disease-associated phenotypes. The compound does not block cAMP elevation induced by the activation of other GPCRs, confirming that E7 does not act on or downstream of heterotrimeric Gαs. It displays dose-dependent inhibition of GPR52-mediated signaling. Gpr52 antagonist E7 shows significant inhibitory effect on WO-459 (100 nM)-induced cAMP elevation in HEK293/GPR52 cells with an IC50 of 12.0 μM. The compound acts as a covalent antagonist against GPR52.
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| ln Vivo |
In vivo, Gpr52 antagonist E7 reduces mutant HTT levels and rescues Huntington's disease-associated phenotypes in cellular and mouse models. The compound rescues HD-associated behavioural phenotypes in a knock-in HD mouse model expressing endogenous mHTT. In Drosophila models, E7 effectively reduces mHTT levels and rescues HD-related phenotypes. The compound is delivered by intracerebroventricular injection for proof-of-concept studies. These data provide proof-of-concept evidence of treating Huntington's disease by reducing soluble mHTT via GPR52 blockade.
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| Enzyme Assay |
GPR52 binding is assessed using in vitro binding assays with HEK293 cells expressing recombinant GPR52. Covalent binding is confirmed by washout experiments (where binding persists after extensive washing) or by mass spectrometry analysis of the receptor-ligand adduct. Activity is evaluated by measuring GPR52-mediated cAMP elevation in response to the agonist WO-459 (100 nM). IC50 values are calculated from dose-response curves using nonlinear regression analysis. Targeted proteomics combined with affinity mass spectrometry is used to identify the binding site and confirm covalent modification.
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| Cell Assay |
Cellular activity is evaluated in HEK293 cells stably or transiently expressing GPR52. Cells are treated with Gpr52 antagonist E7 at various concentrations (typically 0.1-100 μM) and then stimulated with the GPR52 agonist WO-459 (100 nM). cAMP levels are measured by ELISA, HTRF (Cisbio cAMP dynamic kit), or AlphaScreen cAMP detection assays. Mutant HTT levels are measured in HD cellular models by Western blot using antibodies specific for mutant huntingtin (e.g., anti-expanded polyglutamine antibodies such as MW1 or 3B5H10). Huntington's disease-associated phenotypes (e.g., cell death, aggregate formation) are assessed by microscopy or biochemical assays. Selectivity is confirmed by testing against other GPCRs.
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| Animal Protocol |
In vivo efficacy is studied in knock-in Huntington's disease mouse models expressing endogenous mutant HTT. Gpr52 antagonist E7 is administered by intracerebroventricular (i.c.v.) injection for proof-of-concept studies. Mutant HTT levels are measured in brain tissue (striatum, cortex) by Western blot or ELISA using mutant-specific antibodies. Huntington's disease-associated behavioral phenotypes including motor function (rotarod, open field, grip strength) and survival are assessed. The compound rescues HD-associated behavioural phenotypes in knock-in HD mouse models. Gpr52 antagonist E7 has a molecular formula of C20H22O6 and a molecular weight of 358.4 g/mol. CAS Number: 185213-52-9. Appearance: Solid powder. Solubility: DMSO ~125 mg/mL (~348.78 mM). Storage: Powder -20°C for 3 years, 4°C for 2 years; in solvent -80°C for 6 months, -20°C for 1 month. The product requires protection from light.
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| ADME/Pharmacokinetics |
Specific toxicological data for Gpr52 antagonist E7 are not extensively published. As a research compound, it should be handled with standard laboratory safety precautions. The compound is for research use only and not for human or veterinary therapeutic applications. Appropriate personal protective equipment should be used during handling. Avoid inhalation, ingestion, and skin contact. Consult the material safety data sheet (MSDS) for detailed safety information, including potential hazards and disposal considerations.
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| Toxicity/Toxicokinetics |
Gpr52 antagonist E7 is a research tool compound for studying GPR52 biology and Huntington's disease. It is not approved for clinical use. The compound is also known as Isoscabertopin, a sesquiterpene lactone natural product and an anti-cancer ingredient. It acts as an intracellular covalent ligand of orphan receptor GPR52. The discovery of E7 as a specific GPR52 antagonist provides proof-of-concept evidence for treating Huntington's disease by reducing soluble mHTT via GPR52 blockade. E7 acts as a covalent and allosteric ligand with a unique binding mode that cannot fit into the agonist-binding pocket. Reference: Targeted Proteomics Combined with Affinity Mass Spectrometry Analysis Reveals Antagonist E7 Acts As an Intracellular Covalent Ligand of Orphan Receptor GPR52, ACS Chemical Biology (2020).
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| References | |
| Additional Infomation |
Reports indicate that scabertopin has been found in Elephantopus scaber and Elephantopus mollis, and relevant data are available for reference.
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| Molecular Formula |
C20H22O6
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|---|---|
| Molecular Weight |
358.39
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| Exact Mass |
358.141
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| CAS # |
185213-52-9
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| PubChem CID |
21575211
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
592.7±50.0 °C at 760 mmHg
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| Flash Point |
260.5±30.2 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.558
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| LogP |
2.03
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
769
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C/C=C(/C)\C(=O)O[C@H]1CC2=C[C@H](C/C(=C/[C@@H]3[C@@H]1C(=C)C(=O)O3)/C)OC2=O
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| InChi Key |
FTPHYXGWMIZVMP-RZYABJHASA-N
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| InChi Code |
InChI=1S/C20H22O6/c1-5-11(3)18(21)25-16-9-13-8-14(24-20(13)23)6-10(2)7-15-17(16)12(4)19(22)26-15/h5,7-8,14-17H,4,6,9H2,1-3H3/b10-7+,11-5-/t14-,15+,16-,17-/m0/s1
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| Chemical Name |
[(3S,4R,8R,9E,12S)-10-methyl-5-methylidene-6,14-dioxo-7,13-dioxatricyclo[10.2.1.04,8]pentadeca-1(15),9-dien-3-yl] (Z)-2-methylbut-2-enoate
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| Synonyms |
Gpr52 antagonist E7; Gpr-52 antagonist E7; Gpr 52 antagonist E7
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~125 mg/mL (~348.78 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (17.44 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 62.5 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: ≥ 6.25 mg/mL (17.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7903 mL | 13.9513 mL | 27.9026 mL | |
| 5 mM | 0.5581 mL | 2.7903 mL | 5.5805 mL | |
| 10 mM | 0.2790 mL | 1.3951 mL | 2.7903 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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