Nonsteroidal anti-inflammatory drugs, especially selective cyclooxygenase-2 (COX-2) inhibitors, are among the most promising chemopreventive agents for colorectal cancer. However, recent clinical trials have indicated that these inhibitors pose a significantly increased cardiovascular risk. Microsomal prostaglandin E (PGE) synthase-1 (mPGES-1) and mPGES-1-derived PGE2 have gained attention recently as alternative targets to COX-2 for colorectal cancer chemoprevention and chemotherapy. In this review, we summarize the current understanding of the roles of mPGES-1, a PGE2-inactivating enzyme (15-hydroxyprostagladin dehydrogenase), and PGE2 specific receptors (EPs) in colon carcinogenesis.
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http://dx.doi.org/10.1016/j.prostaglandins.2015.06.006 | DOI Listing |
Parasitol Res
January 2025
Department of Parasitology, Chung Shan Medical University, Taichung, 402, Taiwan.
Prostaglandin E2 (PGE-2) is synthesised by cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1). PGE-2 exhibits pro-inflammatory properties in inflammatory conditions. However, there remains limited understanding of the COX-2/mPGES-1/PGE-2 pathway in Angiostrongylus cantonensis-induced meningoencephalitis.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
The inhibition of human microsomal prostaglandin E (PGE) synthase-1 (mPGES-1) is a promising therapeutic modality for developing next-generation anti-inflammatory medications. In this study, we present novel 2-phenylbenzothiazole derivatives featuring heteroaryl sulfonamide end-capping substructures as inhibitors of human mPGES-1, with IC values in the range of 0.72-3.
View Article and Find Full Text PDFNutrients
December 2024
Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed subsp. 557 (LDL557) could significantly decrease OA progression.
View Article and Find Full Text PDFBMC Neurosci
January 2025
Laboratory of Veterinary Internal Medicine, Department of Clinical Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.
Microglia/macrophages participate in the development of and recovery from experimental autoimmune encephalomyelitis (EAE), and the macrophage M1 (pro-inflammatory)/M2 (anti-inflammatory) phase transition is involved in EAE disease progression. We evaluated the efficacy of crisdesalazine (a novel microsomal prostaglandin E2 synthase-1 inhibitor) in an EAE model, including its immune-regulating potency in lipopolysaccharide-stimulated macrophages, and its neuroprotective effects in a macrophage-neuronal co-culture system. Crisdesalazine significantly alleviated clinical symptoms, inhibited inflammatory cell infiltration and demyelination in the spinal cord, and altered the phase of microglial/macrophage and regulatory T cells.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Department of Pharmacy, University of Salerno, Fisciano, Italy.
Inhibiting microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme involved in prostaglandin E (PGE) biosynthesis and tumor microenvironment (TME) homeostasis, is a valuable strategy for treating inflammation and cancer. In this work, 5-methylcarboxamidepyrrole-based molecules were designed and synthesized as new compounds targeting mPGES-1. Remarkably, compounds 1f, 2b, 2c, and 2d were able to significantly reduce the activity of the isolated enzyme, showing IC values in the low micromolar range.
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