WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H522390
CAS#: 439288-66-1
Description: GW627368X is a novel, potent and selective competitive antagonist of prostanoid EP4 receptors with additional human TP receptor affinity. Oral administration of GW627368X showed significant tumor regression characterized by tumor reduction and induction of apoptosis. Reduction in prostaglandin E2 synthesis also led to reduced level of VEGF in plasma. GW627368X will be a valuable tool to explore the role of the prostanoid EP4 receptor in many physiological and pathological settings.
Hodoodo Cat#: H522390
Name: GW627368X
CAS#: 439288-66-1
Chemical Formula: C30H28N2O6S
Exact Mass: 544.17
Molecular Weight: 544.620
Elemental Analysis: C, 66.16; H, 5.18; N, 5.14; O, 17.63; S, 5.89
Synonym: GW627368X; GW 627368X; GW-627368X; GW627368; GW 627368; GW-627368.
IUPAC/Chemical Name: 2-(4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl)-N-(phenylsulfonyl)acetamide
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)
SMILES Code: O=C(NS(=O)(C1=CC=CC=C1)=O)CC2=CC=C(N(CC3=C4C(OCC)=C(C=CC=C5)C5=C3OCC)C4=O)C=C2
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | GW627368 (GW627368X) is a novel, potent and selective competitive antagonist of prostanoid EP4 receptor with additional human TP receptor affinity, with pKi values of 7.0 and 6.8 for human prostanoid EP4 and TP receptors respectively. |
| In vitro activity: | GW627368X inhibits growth in cervical cancer cells by inducing apoptosis was indicated by morphological studies using DAPI/Rhodamine phalloidin staining (Figure 2a). Typical changes in cell morphology including cell shrinkage, disruption of actin filaments, nuclear fragmentation and apoptososme formation was observed. Apoptotic cell death was further confirmed by a timedependent increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive green nuclei (Figure 2b). Reference: Cell Death Dis. 2016 Mar 24;7(3):e2154. https://pubmed.ncbi.nlm.nih.gov/27010855/ |
| In vivo activity: | To evaluate the effect of GW627368X on signaling within tumor environment, the expression profile of various phosphorylated and non-phosphorylated proteins were studied by immunohistochemistry and western blotting (Fig. 3). A significant decrease in phosphorylation level of signaling mediators like EGFR, VEGFR, Akt, MAPK etc was observed with increase in dose of the drug while the total proteins seemed to remain equal in all the sets (Fig. 3D). In addition, highly significant down regulation of COX-2 and EP4 was observed (Fig. 3A). The key player of the cascade, Prostaglandin E2 in plasma and tissue was quantified using enzyme immune assay. The plasma and tissue levels of prostaglandin E-2 drastically reduced from 720.7 ± 11.11pg/ml in control group to 200 ± 0.7076 pg/g in high treatment group vs. 248.8 ± 16.40 pg/ml in normal mice (Fig. 3C). The effect was highly significant. Reference: Cancer Biol Ther. 2015;16(6):922-32. https://pubmed.ncbi.nlm.nih.gov/25894216/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 55.08 | |
| DMF:PBS (pH 7.2) (1:2) | 0.3 | 0.55 | |
| DMSO | 54.8 | 100.66 |
The following data is based on the product molecular weight 544.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Parida S, Pal I, Parekh A, Thakur B, Bharti R, Das S, Mandal M. GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling. Cell Death Dis. 2016 Mar 24;7(3):e2154. doi: 10.1038/cddis.2016.61. PMID: 27010855; PMCID: PMC4823960. 2. Wilson RJ, Giblin GM, Roomans S, Rhodes SA, Cartwright KA, Shield VJ, Brown J, Wise A, Chowdhury J, Pritchard S, Coote J, Noel LS, Kenakin T, Burns-Kurtis CL, Morrison V, Gray DW, Giles H. GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2Hbenzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist. Br J Pharmacol. 2006 Jun;148(3):326-39. doi: 10.1038/sj.bjp.0706726. PMID: 16604093; PMCID: PMC1751567 3. Parida S, Parekh A, Dey G, Ghosh SC, Mandal M. 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. doi: 10.1080/15384047.2015.1040953. Epub 2015 Apr 20. PMID: 25894216; PMCID: PMC4623220. |
| In vitro protocol: | 1. Parida S, Pal I, Parekh A, Thakur B, Bharti R, Das S, Mandal M. GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling. Cell Death Dis. 2016 Mar 24;7(3):e2154. doi: 10.1038/cddis.2016.61. PMID: 27010855; PMCID: PMC4823960. 2. Wilson RJ, Giblin GM, Roomans S, Rhodes SA, Cartwright KA, Shield VJ, Brown J, Wise A, Chowdhury J, Pritchard S, Coote J, Noel LS, Kenakin T, Burns-Kurtis CL, Morrison V, Gray DW, Giles H. GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2Hbenzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist. Br J Pharmacol. 2006 Jun;148(3):326-39. doi: 10.1038/sj.bjp.0706726. PMID: 16604093; PMCID: PMC1751567 |
| In vivo protocol: | 1. Parida S, Parekh A, Dey G, Ghosh SC, Mandal M. 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. doi: 10.1080/15384047.2015.1040953. Epub 2015 Apr 20. PMID: 25894216; PMCID: PMC4623220. Product data sheet MedKoo Biosciences || http://www.medkoo.com || sales@medkoo.com 2500 Gateway Centre Blvd Suite 400, Morrisville, NC27560, USA. Tel: 919-636-5577, Fax: 919-980-4831 2. Wilson RJ, Giblin GM, Roomans S, Rhodes SA, Cartwright KA, Shield VJ, Brown J, Wise A, Chowdhury J, Pritchard S, Coote J, Noel LS, Kenakin T, Burns-Kurtis CL, Morrison V, Gray DW, Giles H. GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2Hbenzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist. Br J Pharmacol. 2006 Jun;148(3):326-39. doi: 10.1038/sj.bjp.0706726. PMID: 16604093; PMCID: PMC1751567 |
1: Parida S, Parekh A, Dey G, Ghosh SC, Mandal M. 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. doi:
10.1080/15384047.2015.1040953. Epub 2015 Apr 20. PubMed PMID: 25894216.
2: Wilson RJ, Giblin GM, Roomans S, Rhodes SA, Cartwright KA, Shield VJ, Brown J,
Wise A, Chowdhury J, Pritchard S, Coote J, Noel LS, Kenakin T, Burns-Kurtis CL,
Morrison V, Gray DW, Giles H. 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):326-39. PubMed PMID: 16604093; PubMed
Central PMCID: PMC1751567.
