Dihydromunduletone (DHM) is a carotenoid analogue that is a selective adhesion G protein-coupled receptor (aGPCR) (GPR56 and GPR114/ADGRG5) antagonist (inhibitor) with an IC 50 value of 20.9 μM for GPR56. However, it does not inhibit GPR110 or class A GPCRs.

Physicochemical Properties

Molecular Formula	C25H28O6
Molecular Weight	424.486227989197
Exact Mass	424.188
CAS #	674786-20-0
PubChem CID	3492326
Appearance	Light yellow to yellow solid powder
LogP	4.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	700
Defined Atom Stereocenter Count	0
InChi Key	RMVZECFNOTWEKD-UHFFFAOYSA-N
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
Chemical Name	1-(3,7-dihydroxy-2,2-dimethyl-3,4-dihydrochromen-6-yl)-2-(5-methoxy-2,2-dimethylchromen-6-yl)ethanone
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	IC50: 20.9 μM (GPR56)[1]; GPR114[1]
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].
References	[1]. Dihydromunduletone Is a Small-Molecule Selective Adhesion G Protein–Coupled Receptor Antagonist. Mol Pharmacol. 2016 Sep; 90(3): 214–224.
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)ethanone is a stilbenoid.

Solubility Data

Solubility (In Vitro)

DMSO: 250 mg/mL (588.94 mM)

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. 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. 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 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	2.3558 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.