Dihydromunduletone

• CAT Number: I017675
• CAS Number: 674786-20-0
• Molecular Formula: C25H28O6
• Molecular Weight: 424.49
• Purity: ≥95%
• Synonyms: 1-(3,7-dihydroxy-2,2-dimethyl-3,4-dihydrochromen-6-yl)-2-(5-methoxy-2,2-dimethylchromen-6-yl)ethanone
• InChI: 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
• InChIKey: RMVZECFNOTWEKD-UHFFFAOYSA-N
• SMILES: CC1(C=CC2=C(O1)C=CC(=C2OC)CC(=O)C3=C(C=C4C(=C3)CC(C(O4)(C)C)O)O)C

Dihydromunduletone (DHM) is a rotenoid derivative and a selective, potent adhesion G protein-coupled receptor (aGPCR) (GPR56 and GPR114/ADGRG5) antagonist with an IC 50 of 20.9 μM for GPR56, but not inhibit GPR110 or class A GPCRs[1].
Assays are initiated by the addition of [35S]GTPγS, and the rates of aGPCR-stimulated G protein activation ([35S]GTPγS binding to Gα) are measured with or without the influence of added compounds. Dihydromunduletone (DHM) inhibits the kinetics of GPR56 7TM-stimulated G13 GTPγS binding to varying degrees. Dihydromunduletone is the best inhibitory compound and reduced the rate at which GPR56 7TM activated G13 >75% (from 0.18 to 0.04 minute−1)[1].
At a concentration of Dihydromunduletone (DHM) that maximally inhibits GPR56 (50 μM), the rate of GPR114 7TM-stimulated Gs activity is also inhibited dramatically. When Dihydromunduletone (50 μM) is applied to the GPR110 7TM, it fails to inhibit GPR110 stimulation of Gq GTPγS binding[1].
Cells transfected with GPR56 A386M 7TM are incubated with increasing concentrations of Dihydromunduletone. P7 peptide agonist is added, and SRE-luciferase activity is measured. Dihydromunduletone inhibits the P7 peptide-induced luciferase activity in a concentration-dependent manner. Cells are also treated with a fixed concentration of 3 µM Dihydromunduletone and then stimulated with an increasing concentration of P7 peptide agonist. Dihydromunduletone treatment blunts P7 peptide activation at each concentration. In conclusion, Dihydromunduletone antagonizes synthetic-peptide agonist and tethered-peptide agonist-mediated aGPCR activation in isolated membranes and HEK293T cell-based assays, but it does not inhibit basal receptor signaling[1].

Reference

[1]. Hannah M. Stoveken, et al. Dihydromunduletone Is a Small-Molecule Selective Adhesion G Protein–Coupled Receptor Antagonist. Mol Pharmacol. 2016 Sep; 90(3): 214–224.
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