GW627368 (also known as GW-627368; GW-627368X) is a novel, orally bioavailable, potent and selective competitive antagonist of prostanoid EP4 receptor with anticancer activity. It demonstrates additional affinity for the human TP receptor, as evidenced by pKi values of 6.8 for the human prostanoid TP receptor and 7.0 for the human EP4 receptor. Significant tumor regression in GW627368X was demonstrated, with tumor reduction and apoptosis induction. Lower levels of VEGF in plasma were also caused by a decrease in prostaglandin E2 synthesis. In order to investigate the function of the prostanoid EP4 receptor in a variety of physiological and pathological contexts, GW627368X will be an invaluable resource.
Physicochemical Properties
| Molecular Formula | C30H28N2O6S |
| Molecular Weight | 544.6181 |
| Exact Mass | 544.166 |
| Elemental Analysis | C, 66.16; H, 5.18; N, 5.14; O, 17.63; S, 5.89 |
| CAS # | 439288-66-1 |
| PubChem CID | 5312130 |
| Appearance | White to off-white solid powder |
| Density | 1.3±0.1 g/cm3 |
| Index of Refraction | 1.645 |
| LogP | 4.95 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 39 |
| Complexity | 953 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(C1C([H])=C([H])C([H])=C([H])C=1[H])(N([H])C(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])N1C(C2=C(C3=C([H])C([H])=C([H])C([H])=C3C(=C2C1([H])[H])OC([H])([H])C([H])([H])[H])OC([H])([H])C([H])([H])[H])=O)=O)(=O)=O |
| InChi Key | XREWXJVMYAXCJV-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C30H28N2O6S/c1-3-37-28-23-12-8-9-13-24(23)29(38-4-2)27-25(28)19-32(30(27)34)21-16-14-20(15-17-21)18-26(33)31-39(35,36)22-10-6-5-7-11-22/h5-17H,3-4,18-19H2,1-2H3,(H,31,33) |
| Chemical Name | N-(benzenesulfonyl)-2-[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)phenyl]acetamide |
| Synonyms | GW 627368X; GW 627368; GW627368X; GW627368; GW-627368X; GW-627368 |
| 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 | EP |
| ln Vitro | GW627368 (GW627368 GW627368 (GW627368 X) (10 μM) inhibits 100% of U-46619 (EC100)-induced GW627368 (GW627368 [1]. GW627368 (GW627368 |
| ln Vivo | GW627368 (GW627368 Animal model: 6-8 weeks old Swiss albino mice [3] Dosage: 0 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, 15 mg/kg Administration method: Orally, once every other day, continuously 28-day results: showed potential for anti-tumor and anti-proliferative effects in sarcoma 180-bearing mice. |
| Animal Protocol |
6-8 weeks Swiss albino mice 0 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, 15 mg/kg Oral administration, every alternate day for 28 days |
| References |
[1]. GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist. Br J Pharmacol. 2006 Jun;148(3 [2]. Molecular and pharmacological blockade of the EP4 receptor selectively inhibits both proliferation and invasion of human inflammatory breast cancer cells. J Exp Ther Oncol. 2008;7(4):299-312. [3]. Molecular inhibition of prostaglandin E2 with GW627368X: Therapeutic potential and preclinical safety assessment in mouse sarcoma model. Cancer Biol Ther. 2015;16(6):922-32. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~100 mg/mL (~183.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.59 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 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 (4.59 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 | 1.8361 mL | 9.1807 mL | 18.3614 mL | |
| 5 mM | 0.3672 mL | 1.8361 mL | 3.6723 mL | |
| 10 mM | 0.1836 mL | 0.9181 mL | 1.8361 mL |