| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 20.9 μM (GPR56)[1]; GPR114[1]
GPR56 (ADGRG1) and GPR114 (ADGRG5). Dihydromundulone is a selective antagonist of these adhesion G protein-coupled receptors (aGPCRs). It has an IC50 of approximately 20.9 microM (21 microM) for GPR56. It does not inhibit GPR110 or Class A GPCRs, demonstrating selectivity within the aGPCR family. These receptors are involved in tumor suppression (GPR56) and immune cell regulation (GPR114/ADGRG5). |
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| ln Vitro |
[35S]GTPηS is added to start assays, and rates of aGPCR-stimulated G protein activation ([35S]GTPηS binding to Gα) are measured with and without the presence of additional compounds. To differing degrees, GPR56 7TM-stimulated G13 GTPγS binding kinetics are inhibited by dihydromunduletone (DHM). With a reduction in GPR56 7TM activated G13 >75% (from 0.18 to 0.04 minutes−1), dihydromunduletone is the best inhibitory compound[1]. The rate of GPR114 7TM-stimulated Gs activity is also significantly inhibited at a concentration of Dihydromunduletone (DHM) that maximally inhibits GPR56 (50 μM). Dihydromunduletone (50 μM) does not prevent GPR110 stimulation of Gq GTPηS binding when it is applied to the GPR110 7TM[1]. Dihydromunduletone is incubated at escalating concentrations in cells transfected with GPR56 A386M 7TM. SRE-luciferase activity is assessed after the addition of P7 peptide agonist. In a concentration-dependent manner, dihydromunduletone inhibits the P7 peptide-induced luciferase activity. Additionally, cells are exposed to a fixed concentration of 3 µM dihydromunduletone before being stimulated with progressively higher concentrations of P7 peptide agonist. At every concentration, P7 peptide activation is blunted by dihydromunduletone treatment. As a result, in isolated membranes and HEK293T cell-based experiments, dihydromunduletone opposes synthetic-peptide agonist and tethered-peptide agonist-mediated aGPCR activation, but it does not impede basal receptor signaling[1].
Dihydromundulone inhibits the activation of GPR56 and GPR114/ADGRG5 by their tethered agonists. The in vitro activity has been characterized in cell-based assays measuring receptor activation. It does not inhibit other aGPCRs such as GPR110 or conventional Class A GPCRs, indicating selectivity. Detailed quantitative in vitro efficacy data (EC50/IC50 beyond the reported 20.9 microM for GPR56) is limited, but it is established as a selective antagonist chemical probe. |
| ln Vivo |
As a selective antagonist of aGPCRs, Dihydromundulone is used as a chemical tool to study the in vivo functions of GPR56 and GPR114. These receptors are implicated in tumor suppression (GPR56) and immune cell regulation (GPR114/ADGRG5). Specific in vivo efficacy data for DHM is not detailed in standard literature, but it is designed to dissect the physiological and pathological roles of these receptors in animal models of cancer and immunity.
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| Enzyme Assay |
A standard non-cellular binding assay for aGPCRs such as GPR56 is challenging due to their large size and complex activation mechanism. Dihydromundulone's activity is typically confirmed in cellular assays rather than cell-free enzyme binding assays. One potential approach is a surface plasmon resonance (SPR) assay using purified aGPCR extracellular domains to study direct interaction, but this is not a standard protocol for this compound.
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| Cell Assay |
Dihydromundulone's activity is typically validated using reporter gene assays in cells overexpressing the target receptors. For example, HEK293 cells are co-transfected with a GPR56 or GPR114/ADGRG5 expression plasmid and a CRE- or SRE-luciferase reporter. Cells are treated with the receptor's tethered agonist or control, in the presence or absence of varying concentrations of DHM. Luminescence is measured, and the IC50 for antagonism is calculated. This confirms functional inhibition of the receptor signaling pathway.
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| Animal Protocol |
For in vivo studies, animal models (typically mice) are used to study the role of GPR56 in cancer. Xenograft tumors are established using cell lines with or without GPR56 expression. Dihydromundulone is then administered to the mice, often via intraperitoneal (IP) injection, with dosing regimens determined by the researcher. Tumor volume and metastasis are monitored. Endpoints also include assessment of immune cell infiltration and function to study GPR114/ADGRG5.
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| ADME/Pharmacokinetics |
Dihydromundulone is a small, lipophilic molecule (MW 424.49). For in vivo administration, it is typically formulated in vehicles such as DMSO, PEG300, Tween 80, and saline (e.g., 5% DMSO, 40% PEG300, 5% Tween-80, 50% ddH2O) to ensure solubility. Specific pharmacokinetic parameters such as half-life, oral bioavailability, and clearance are not detailed in standard research sources, as it is used as a chemical probe. Limited water solubility may be a consideration.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Dihydromundulone is not available in standard research resources. As a potent inhibitor of aGPCRs, its on-target toxicity would be related to the biological functions of GPR56 and GPR114/ADGRG5. In research settings, it has been used in vivo without reports of acute toxicity at the doses used for target validation. Comprehensive toxicological profiling would be required for any potential therapeutic development, but the compound is intended for preclinical use only.
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| References | |
| Additional Infomation |
1-(3,7-dihydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-6-yl)-2-(5-methoxy-2,2-dimethyl-1-benzopyran-6-yl) acetone is a stilbene compound.
Dihydromundulone is a research chemical probe used to study the biology of adhesion G-protein coupled receptors (aGPCRs), specifically GPR56 and GPR114. It is a selective antagonist that helps dissect the signaling pathways and physiological roles of these receptors, which are challenging to study due to their complex activation by tethered agonists. The compound is not approved for any therapeutic use and is strictly for preclinical research. |
| Molecular Formula |
C25H28O6
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|---|---|
| Molecular Weight |
424.486227989197
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| Exact Mass |
424.188
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| CAS # |
674786-20-0
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| PubChem CID |
3492326
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
700
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(C=CC2=C(O1)C=CC(=C2OC)CC(=O)C3=C(C=C4C(=C3)CC(C(O4)(C)C)O)O)C
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| InChi Key |
RMVZECFNOTWEKD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H28O6/c1-24(2)9-8-16-20(30-24)7-6-14(23(16)29-5)11-18(26)17-10-15-12-22(28)25(3,4)31-21(15)13-19(17)27/h6-10,13,22,27-28H,11-12H2,1-5H3
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| Chemical Name |
1-(3,7-dihydroxy-2,2-dimethyl-3,4-dihydrochromen-6-yl)-2-(5-methoxy-2,2-dimethylchromen-6-yl)ethanone
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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 (588.94 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.90 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 (4.90 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 (4.90 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 | 2.3558 mL | 11.7788 mL | 23.5577 mL | |
| 5 mM | 0.4712 mL | 2.3558 mL | 4.7115 mL | |
| 10 mM | 0.2356 mL | 1.1779 mL | 2.3558 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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