(±)-Aiphanol is a newly discovered stilbenolignan compound. (±)-Aiphanol has significant anti-inflammatory activity by inhibiting COX-1 and COX-2. Its inhibitory effect on COX-1 is particularly strong (IC50 = 1.9 μM), while its effect on COX-2 is relatively weak (IC50= 9.9 μM). (±)-Aiphanol potently inhibits VEGFR2 (IC50=0.92 µM). (±)-Aiphanol blocks angiogenesis and promotes cell apoptosis by inhibiting the activities of VEGFR2 and COX2. (±)-Aiphanol is available orally.

Physicochemical Properties

Molecular Formula	C25H24O8
Molecular Weight	452.45
Exact Mass	452.147
CAS #	578020-29-8
PubChem CID	10366595
Appearance	Typically exists as solid at room temperature
LogP	3.7
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	6
Heavy Atom Count	33
Complexity	620
Defined Atom Stereocenter Count	2
SMILES	O1C2C=C(/C=C/C3C=C(C=C(C=3)O)O)C=CC=2O[C@H](CO)[C@H]1C1C=C(C(=C(C=1)OC)O)OC
InChi Key	KDMFHGGHQLUIRH-OOODPRFPSA-N
InChi Code	InChI=1S/C25H24O8/c1-30-21-10-16(11-22(31-2)24(21)29)25-23(13-26)32-19-6-5-14(9-20(19)33-25)3-4-15-7-17(27)12-18(28)8-15/h3-12,23,25-29H,13H2,1-2H3/b4-3+/t23-,25-/m1/s1
Chemical Name	5-[(E)-2-[(2R,3R)-3-(4-hydroxy-3,5-dimethoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethenyl]benzene-1,3-diol
Synonyms	Aiphanol
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	COX-1 1.9 μM (IC50) COX-2 9.9 μM (IC50) VEGFR2 0.92 μM (IC50)
ln Vitro	(±)-Aiphanol (7.5-30 μM; 6 h) inhibits VEGF-induced neovascularization in HUVECs in a dose-dependent manner. It significantly reduces the levels of PGE2 and VEGF in HUVECs, an effect that disappears after COX2 silencing. It is more potent than Celecoxib (HY-14398) in inhibiting VEGF-induced tubular structure formation in HUVECs[2]. (±)-Aiphanol (7.5-30 μM; 6h) significantly inhibits microvascular growth in CAM, with an effect comparable to that of Bevacizumab (HY-P9906)[2]. (±)-Aiphanol inhibits the activity of VEGFR3/FLT4, VEGFR2/KDR, and VEGFR1/FLT1, and has moderate or weak inhibitory effects on certain kinases in the PI3K-AKT and MAPK pathways[2]. (±)-Aiphanol (30 μM; 24 h) inhibited the proliferation of HUVECs and induced cell apoptosis[2].
ln Vivo	(±)-Aiphanol (30 mg/kg; po; single dose) significantly inhibits tumor growth and significantly reduces tumor weight in the MC38 syngeneic mouse model [2].
Cell Assay	Apoptosis Analysis[2] Cell Types: HUVECs Concentration: 30 μM Incubation Duration: 24 h Experimental Results: Did not cause significant changes in cell cycle distribution but significantly increased apoptosis. Elevated the expression of P53 and BAX proteins.
Animal Protocol	Animal/Disease Models:MC38 syngeneic mouse model[2] Doses: 30 mg/kg Route of Administration: p.o.; single dose Experimental Results: Increased apoptosis in tumor tissues and reduced the phosphorylation levels of VEGFR2, AKT, and ERK. Significantly decreased the levels of vascular markers CD31 and factor VIII. Lowered the levels of PGE2 in plasma and VEGF in tumor tissues. Did not cause changes in body weight or the morphology of major organs.
References	[1]. Total Synthesis of (.+-.)-Aiphanol, a Novel Cyclooxygenase-inhibitory Stilbenolignan[J]. Chemistry letters, 2003, 32(5): 420-421. [2]. Aiphanol, a native compound, suppresses angiogenesis via dual-targeting VEGFR2 and COX2. Signal Transduct Target Ther. 2021 Dec 3;6(1):413.
Additional Infomation	Aiphanol is a lignan that is (2R)-2,3-dihydro-1,4-benzodioxin-2-ylmethanol which is substituted by a 2-(3,5-dihydroxyphenyl)ethenyl group at position 6 and a 4-hydroxy-3,5-dimethoxyphenyl group at position 3. It is a stilbenolignan isolated from the seeds of Aiphanes aculeata and exhibits potent inhibitory efficacy against cyclooxygenase-1 and -2 (COX-1 and COX-2). It has a role as an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor. It is a stilbenoid, a lignan, an aromatic ether and a benzodioxine. Aiphanol has been reported in Aiphanes horrida with data available.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2102 mL	11.0509 mL	22.1019 mL
	5 mM	0.4420 mL	2.2102 mL	4.4204 mL
	10 mM	0.2210 mL	1.1051 mL	2.2102 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.