SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4- dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid, is a selective, orally active, LTB4 receptor antagonist currently in clinical trials for psoriasis and ulcerative colitis. Exhaustive SAR studies found a potential backup compound, SC-50605, which was 7-16 times more potent than SC-41930 in LTB4 receptor binding, chemotaxis and degranulation assays. SC-50605 also inhibited LTB4-induced intradermal chemotaxis in cavine skin at an oral dose of 0.10 mg/kg and displayed good activity in animal models of colitis and epidermal inflammation both orally and topically.
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http://dx.doi.org/10.1007/BF01972705 | DOI Listing |
Curr Ther Res Clin Exp
November 2024
Laboratorio de Oncología Celular y Molecular. Departamento de Oncología Básico-Clínica. Facultad de Medicina. Universidad de Chile, Santiago, Chile.
Background: Leukotriene B (LTB) plays a crucial role in carcinogenesis by inducing epithelial-mesenchymal transition (EMT), a process associated with tumor progression. The synthesis of LTB is mediated by leukotriene A hydrolase (LTAH), and it binds to the receptors BLT and BLT. Dysregulation in LTB production is linked to the development of various pathologies.
View Article and Find Full Text PDFSci Adv
January 2025
Fels Cancer Institute for Personalized Medicine, Department of Cancer & Cellular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.
View Article and Find Full Text PDFJ Med Chem
January 2025
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, and Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, Frankfurt am Main 60596, Germany.
The leukotriene B4 receptor 2 (BLT2) is a G-protein coupled receptor, which is endogenously activated by 12()-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT). BLT2 is gaining attention as a potential therapeutic target involved in various pathologies including diabetic wound healing, ophthalmic diseases, and colitis. However, validation of BLT2 as drug target requires chemical probes and pharmacological tools which will allow for application in vivo.
View Article and Find Full Text PDFJ Vet Res
December 2024
Division of Reproductive Biology, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10-748 Olsztyn, Poland.
Introduction: Endometritis is a very common pathology in animals which changes endometrial leukotriene (LT) formation and muscarinic 2 and 3 receptor subtypes (M2R/M3R) and α-7 nicotinic acetylcholine (ACh) receptor (α-7 nAChR) expression patterns. With the relationship between ACh, its receptors and LT production remaining unclear, the role of M2R, M3R and α-7 nAChR in action of ACh on the 5-lipoxygenase (5-LO), LTA4 hydrolase (LTAH) and LTC4 synthase (LTCS) protein abundances in the inflamed porcine endometrium and on the tissue secretion of LTB4 and LTC4 were studied.
Material And Methods: On day three of the oestrous cycle in gilts aged 7-8 months, 50 mL of either saline solution (control group, n = 5) or an suspension at 10 colony-forming units/mL ( group, n = 5), was injected into each uterine horn.
Arch Toxicol
December 2024
Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, 26505, USA.
Exposure to fibrogenic multi-walled carbon nanotubes (MWCNTs) induces the production of proinflammatory lipid mediators (LMs) in myeloid cells to instigate inflammation. The molecular underpinnings of LM production in nanotoxicity remain unclear. Here we report that PU.
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