Matches in SemOpenAlex for { <https://semopenalex.org/work/W2002887511> ?p ?o ?g. }
Showing items 1 to 80 of
80
with 100 items per page.
- W2002887511 abstract "Chronic inflammation is associated with 25% of all cancers. In the inflammation-cancer axis, prostaglandin E2 (PGE2) is one of the major players involved. Prostaglandin E synthase (PGES) is an enzyme downstream of the cyclooxygenases (COXs) in the PGE2 biosynthesis pathway. Among the three PGES isoforms, microsomal prostaglandin E synthase-1 (mPGES-1) is inducible by proinflammatory stimuli and constitutively expressed in colon, lung, and gastric cancers. The potential role for this enzyme in tumorigenesis has also been reported. Since inhibition of COXs may lead to some side effects due to the global reduction of other key prostaglandins, targeting downstream mPGES-1 might be a better therapeutic or chemopreventive strategy for cancers. In order to identify novel small molecule inhibitors of mPGES-1, we have screened in silico a small library of compounds. As a result, 14 lead compounds were identified by molecular docking simulations of the chemicals based on the crystal structure of mPGES-1. These compounds were tested for their ability to inhibit cell growth, induce apoptosis and decrease cytokine-stimulated PGE2 production in various colorectal and lung cancer cell lines. Using surface plasmon resonance (SPR) spectroscopy, we show the binding of the compounds PGE001 and PGE011 to human mPGES-1 recombinant protein with good affinity (KD at low micromolar range). These two compounds also showed the ability to reduce the IL-1beta-induced PGE2 production in HT29 and SW837 colon cancer cells and A549 lung cancer cell line with EC50 at low micromolar range. Furthermore, the compounds exhibit significant anti-tumor activity in the SW837 xenograft mouse model with T/C (relative size of treated and control tumors)=40.3% for compound PGE001 and T/C=68.7% for compound PGE011 (P Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3565." @default.
- W2002887511 created "2016-06-24" @default.
- W2002887511 creator A5007898685 @default.
- W2002887511 creator A5018260058 @default.
- W2002887511 creator A5025340449 @default.
- W2002887511 creator A5067748893 @default.
- W2002887511 creator A5070590221 @default.
- W2002887511 creator A5071627942 @default.
- W2002887511 creator A5084404621 @default.
- W2002887511 date "2010-04-15" @default.
- W2002887511 modified "2023-09-25" @default.
- W2002887511 title "Abstract 3565: Novel inhibitors of mPGES-1 exhibit anti-tumor activity in colorectal and lung cancers" @default.
- W2002887511 doi "https://doi.org/10.1158/1538-7445.am10-3565" @default.
- W2002887511 hasPublicationYear "2010" @default.
- W2002887511 type Work @default.
- W2002887511 sameAs 2002887511 @default.
- W2002887511 citedByCount "0" @default.
- W2002887511 crossrefType "proceedings-article" @default.
- W2002887511 hasAuthorship W2002887511A5007898685 @default.
- W2002887511 hasAuthorship W2002887511A5018260058 @default.
- W2002887511 hasAuthorship W2002887511A5025340449 @default.
- W2002887511 hasAuthorship W2002887511A5067748893 @default.
- W2002887511 hasAuthorship W2002887511A5070590221 @default.
- W2002887511 hasAuthorship W2002887511A5071627942 @default.
- W2002887511 hasAuthorship W2002887511A5084404621 @default.
- W2002887511 hasConcept C121608353 @default.
- W2002887511 hasConcept C126322002 @default.
- W2002887511 hasConcept C164027704 @default.
- W2002887511 hasConcept C185592680 @default.
- W2002887511 hasConcept C190283241 @default.
- W2002887511 hasConcept C2776914184 @default.
- W2002887511 hasConcept C2777956040 @default.
- W2002887511 hasConcept C2780664492 @default.
- W2002887511 hasConcept C502942594 @default.
- W2002887511 hasConcept C55493867 @default.
- W2002887511 hasConcept C555283112 @default.
- W2002887511 hasConcept C62112901 @default.
- W2002887511 hasConcept C71924100 @default.
- W2002887511 hasConcept C98274493 @default.
- W2002887511 hasConceptScore W2002887511C121608353 @default.
- W2002887511 hasConceptScore W2002887511C126322002 @default.
- W2002887511 hasConceptScore W2002887511C164027704 @default.
- W2002887511 hasConceptScore W2002887511C185592680 @default.
- W2002887511 hasConceptScore W2002887511C190283241 @default.
- W2002887511 hasConceptScore W2002887511C2776914184 @default.
- W2002887511 hasConceptScore W2002887511C2777956040 @default.
- W2002887511 hasConceptScore W2002887511C2780664492 @default.
- W2002887511 hasConceptScore W2002887511C502942594 @default.
- W2002887511 hasConceptScore W2002887511C55493867 @default.
- W2002887511 hasConceptScore W2002887511C555283112 @default.
- W2002887511 hasConceptScore W2002887511C62112901 @default.
- W2002887511 hasConceptScore W2002887511C71924100 @default.
- W2002887511 hasConceptScore W2002887511C98274493 @default.
- W2002887511 hasLocation W20028875111 @default.
- W2002887511 hasOpenAccess W2002887511 @default.
- W2002887511 hasPrimaryLocation W20028875111 @default.
- W2002887511 hasRelatedWork W142574607 @default.
- W2002887511 hasRelatedWork W1784896684 @default.
- W2002887511 hasRelatedWork W1980101293 @default.
- W2002887511 hasRelatedWork W1989256917 @default.
- W2002887511 hasRelatedWork W2005055360 @default.
- W2002887511 hasRelatedWork W2022917812 @default.
- W2002887511 hasRelatedWork W2023791568 @default.
- W2002887511 hasRelatedWork W2025069231 @default.
- W2002887511 hasRelatedWork W2026563687 @default.
- W2002887511 hasRelatedWork W2071078831 @default.
- W2002887511 hasRelatedWork W2091907630 @default.
- W2002887511 hasRelatedWork W2109942391 @default.
- W2002887511 hasRelatedWork W2120859709 @default.
- W2002887511 hasRelatedWork W2143896607 @default.
- W2002887511 hasRelatedWork W2292223642 @default.
- W2002887511 hasRelatedWork W2313095757 @default.
- W2002887511 hasRelatedWork W2487533997 @default.
- W2002887511 hasRelatedWork W2761604906 @default.
- W2002887511 hasRelatedWork W2884357477 @default.
- W2002887511 hasRelatedWork W3048978270 @default.
- W2002887511 isParatext "false" @default.
- W2002887511 isRetracted "false" @default.
- W2002887511 magId "2002887511" @default.
- W2002887511 workType "article" @default.