Tris(2,4-di-tert-butylphenyl)phosphate is a bioactive compound extracted from Vitex negundo L. that displays anti~inflammatory activity and inhibits secreted phospholipase A2 (sPLA2) through molecular docking.

Physicochemical Properties

Molecular Formula	C42H63O4P
Molecular Weight	662.92099404335
Exact Mass	662.446
Elemental Analysis	C, 76.10; H, 9.58; O, 9.65; P, 4.67
CAS #	95906-11-9
PubChem CID	14572930
Appearance	White to off-white solid powder
Melting Point	99-101 °C(lit.)
LogP	13.116
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	12
Heavy Atom Count	47
Complexity	920
Defined Atom Stereocenter Count	0
SMILES	O=P(OC1C(C(C)(C)C)=CC(C(C)(C)C)=CC=1)(OC1C(C(C)(C)C)=CC(C(C)(C)C)=CC=1)OC1C(C(C)(C)C)=CC(C(C)(C)C)=CC=1
InChi Key	AZSKHRTUXHLAHS-UHFFFAOYSA-N
InChi Code	InChI=1S/C42H63O4P/c1-37(2,3)28-19-22-34(31(25-28)40(10,11)12)44-47(43,45-35-23-20-29(38(4,5)6)26-32(35)41(13,14)15)46-36-24-21-30(39(7,8)9)27-33(36)42(16,17)18/h19-27H,1-18H3
Synonyms	AAN06119; AAN-06119; AAN 06119;
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	sPLA2/secretory Phospholipase A2
ln Vitro	Novel compounds with significant medicinal properties have gained much interest in therapeutic approaches for treating various inflammatory disorders like arthritis, odema and snake bites and the post-envenom (impregnating with venom) consequences. Inflammation is caused by the increased concentration of secretory Phospholipases A(2) (sPLA(2)s) at the site of envenom. A novel compound Tris(2,4-di-tert-butylphenyl) phosphate (TDTBPP) was isolated from the leaves of Vitex negundo and the crystal structure was reported recently[1].
ln Vivo	In a carrageenan-induced foot edema model, tris(2,4-di-tert-butylphenyl)phosphate (TDTBPP; 50 mg/kg and 70 mg/kg) has strong anti-inflammatory efficacy [1]. Phosphate tris(2,4-di-tert-butylphenyl) (50 mg/kg and 70 mg/kg) has the ability to considerably lower raw claw edema volume [1].
Animal Protocol	The acute anti-inflammatory activity of TDTBPP was assessed by Carrageenan-induced rat paw odema method. TDTBPP reduced the raw paw odema volume significantly at the tested doses of 50 mg/kg and 70 mg/kg body weight. Molecular docking studies were carried out with the X-ray crystal structures of Daboia russelli pulchella's (Vipera russelli, Indian Russell's viper) venom sPLA(2) and Human non-pancreatic secretory PLA(2) (Hnps PLA(2)) as targets to illustrate the antiinflammatory and antidote activities of TDTBPP. Docking results showed hydrogen bond (H-bond) interaction with Lys69 residue lying in the anti-coagulant loop of D. russelli's venom PLA(2), which is essential in the catalytic activity of the enzyme and hydrophobic interactions with the residues at the binding site (His48, Asp49). Docking of TDTBPP with Hnps PLA(2) structure showed coordination with calcium ion directly as well as through the catalytically important water molecule (HOH1260) located at the binding site[1].
References	[1]. Active compound from the leaves of Vitex negundo L. shows anti-inflammatory activity with evidence of inhibition for secretory Phospholipase A(2) through molecular docking. Bioinformation. 2011;7(4):199-206.
Additional Infomation	Tris(2,4-di-tert-butylphenyl) phosphate is an aryl phosphate.

Solubility Data

Solubility (In Vitro)

Ethanol : ~100 mg/mL (~150.85 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (3.77 mM) in 10% EtOH + 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 EtOH 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 (3.77 mM) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH 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: ≥ 2.5 mg/mL (3.77 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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	1.5085 mL	7.5424 mL	15.0848 mL
	5 mM	0.3017 mL	1.5085 mL	3.0170 mL
	10 mM	0.1508 mL	0.7542 mL	1.5085 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.