GSK726701A is a partial agonist of prostaglandin E2 receptor 4 (EP4) with pEC50 of 7.4.

Physicochemical Properties

Molecular Formula	C24H22FNO5
Molecular Weight	423.43359041214
Exact Mass	423.148
CAS #	945721-87-9
PubChem CID	16678098
Appearance	White to off-white solid powder
LogP	4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	31
Complexity	660
Defined Atom Stereocenter Count	0
SMILES	O=C(CC1C(F)=CC(N2CC3C(=C(C4C(C=3OCC)=CC=CC=4)OCC)C2=O)=CC=1)O
InChi Key	YJEFCZJZEASKIO-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H22FNO5/c1-3-30-22-16-7-5-6-8-17(16)23(31-4-2)21-18(22)13-26(24(21)29)15-10-9-14(11-20(27)28)19(25)12-15/h5-10,12H,3-4,11,13H2,1-2H3,(H,27,28)
Chemical Name	2-[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-2-fluorophenyl]acetic acid
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

ln Vitro	GSK726701A exhibits no discernible activity against a wider variety of targets and is extremely selective (>100-fold) against a panel of additional prostaglandin receptors (EP1-3, DP1, FP, IP, TP). In a human whole blood (HWB) experiment, it showed EP4 agonist action with equal potency and intrinsic activity (pEC50=8.2), blocking LPS-mediated TNFα production [1].
ln Vivo	There is strong pharmacokinetic evidence for GSK726701A in rats, dogs, and monkeys. Animal models of inflammatory and neuropathic pain are highly responsive to GSK726701A. At a dose of 3 mg/kg, which is comparable to the clinical gold standard of 30 mg/kg gabapentin, GSK726701A totally reverses mechanical allodynia caused by CCI. In the FCA acute inflammatory pain rat model, GSK726701A has an ED50 of 0.2 mg/kg[1].
References	[1]. Discovery of {4-[4,9-bis(ethyloxy)-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-2-fluorophenyl}acetic acid (GSK726701A), a novel EP4 receptor partial agonist for the treatment of pain. Bioorg Med Chem Lett. 2018 Jun 1;28(10):1892-1896.

Solubility Data

Solubility (In Vitro)

DMSO : ~25 mg/mL (~59.04 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.90 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 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	2.3617 mL	11.8083 mL	23.6167 mL
	5 mM	0.4723 mL	2.3617 mL	4.7233 mL
	10 mM	0.2362 mL	1.1808 mL	2.3617 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.