Embelin is a naturally occurring quinone compound that was isolated from the Japanese herb Ardisia. It has anti-tumor and anti-inflammatory properties, and it also functions as a powerful and cell-permeable inhibitor of XIAP (X-linked inhibitor of apoptosis), with an IC50 value of 4.1 μM in cell-free assays.

Physicochemical Properties

Molecular Formula	C17H26O4
Molecular Weight	294.39
Exact Mass	294.183
Elemental Analysis	C, 69.36; H, 8.90; O, 21.74
CAS #	550-24-3
Related CAS #	550-24-3
PubChem CID	3218
Appearance	Yellow to orange solid powder
Density	1.131
Boiling Point	431.9±45.0 °C at 760 mmHg
Melting Point	145-146 ºC
Flash Point	229.1±25.2 °C
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.538
LogP	5.7
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	10
Heavy Atom Count	21
Complexity	432
Defined Atom Stereocenter Count	0
SMILES	O([H])C1C(C([H])=C(C(C=1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)O[H])=O
InChi Key	IRSFLDGTOHBADP-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H26O4/c1-2-3-4-5-6-7-8-9-10-11-13-16(20)14(18)12-15(19)17(13)21/h12,18,21H,2-11H2,1H3
Chemical Name	2,5-dihydroxy-3-undecylcyclohexa-2,5-diene-1,4-dione
Synonyms	Embelic acid; NSC91874; NSC91874; Embelin; NSC 91874; Emberine
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 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)

Biological Activity

Targets	5-LO (IC50 = 0.06 μM); mPGES-1 (IC50 = 0.2 μM); XIAP (IC50 = 4.1 μM)
ln Vitro	Embelin from the Japanese Ardisia herb is a small-molecular inhibitor that binds to the XIAP BIR3 domain with which Smac and caspsase-9 bind. Embelin has IC50 values of 3.7 and 5.7 μM and inhibits PC-3 and LNCap cell growth in a dose-dependent manner. While Embelin's toxicity in normal PrEC and WI-38 cells is much lower, with IC50 values of 20.1 μM and 19.3 μM, respectively. When PC-3 cells are treated for 48 hours with 25 and 50 μM of embelin, 30% and 75% of the cells die, which is an increase of about 3 and 9 times more than in untreated cells.[1] Embelin selectively inhibits 5-lipoxygenase (5-LO) and Microsomal prostaglandin E2 synthase-1 (mPGES-1) with IC50 values of 0.06 and 0.2 mM, respectively, to suppress the biosynthesis of eicosanoids.[2]
ln Vivo	Embelin has also been used extensively in various animal models to study the role of XIAP. In the azoxymethane/dextran sulfate sodium (AOM/DSS) induced colitis-associated cancer (CAC) model, embelin reduced both incidence and tumor size in mice by inhibiting proliferation of tumor epithelial cells and suppressing IL6 expression and IL6-activated STAT3 in vivo.
Enzyme Assay	Fluorescence polarization experiments are performed in Dynex 96-well, black, round-bottom plates. A final volume of 125 L is created by adding a 5 μL sample of Embelin dilutions in DMSO, preincubated XIAP BIR3 protein (0.06 M), and the N terminus of a Smac peptide (SM7F) (0.01 M) in the assay buffer. Both the bound peptide control (equivalent to 0% inhibition) and the free peptide control (equivalent to 100% inhibition) were used in each assay. The bound peptide control contained XIAP BIR3 protein and SM7F. To achieve equilibrium, the plates were combined and incubated for 3 hours at room temperature.
Cell Assay	The MTT-based assay, which uses Cell Proliferation Reagent WST-1 in accordance with the manufacturer's instructions, is used to measure cell growth. Cells (5000 cells/well) are grown in medium containing 10% FBS and different concentrations of Embelin. WST-1 is added to each well and incubated for 1-3 hours at 37 °C four to five days later. A plate reader is used to measure absorbance at 450 nm with a correction at 650 nm.
Animal Protocol	50 mg/kg/day; p.o. AOM/DSS-induced colitis-associated cancer (CAC) model
References	[1]. J Med Chem . 2004 May 6;47(10):2430-40. [2]. Biochem Pharmacol . 2013 Aug 15;86(4):476-86.
Additional Infomation	Embelin is a member of the class of dihydroxy-1,4-benzoquinones that is 2,5-dihydroxy-1,4-benzoquinone which is substituted by an undecyl group at position 3. Isolated from Lysimachia punctata and Embelia ribes, it exhibits antimicrobial, antineoplastic and inhibitory activity towards hepatitis C protease. It has a role as a hepatitis C protease inhibitor, an antimicrobial agent, an antineoplastic agent and a plant metabolite. Embelin has been reported in Embelia schimperi, Ardisia paniculata, and other organisms with data available.

Solubility Data

Solubility (In Vitro)

DMSO: ~59 mg/mL (~200.4 mM) Water: <1 mg/mL (slightly soluble or insoluble) Ethanol: ~12 mg/mL (~40.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (8.49 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (8.49 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 25.0 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	3.3969 mL	16.9843 mL	33.9685 mL
	5 mM	0.6794 mL	3.3969 mL	6.7937 mL
	10 mM	0.3397 mL	1.6984 mL	3.3969 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.