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.

Download full-text PDF

Source
http://dx.doi.org/10.1007/BF01972705DOI Listing

Publication Analysis

Top Keywords

ltb4 receptor
12
design synthesis
4
synthesis second
4
second generation
4
generation leukotriene
4
leukotriene ltb4
4
receptor antagonists
4
antagonists sc-41930
4
sc-41930 sc-41930
4
sc-41930 7-[3-4-acetyl-3-methoxy-2-propylphenoxypropoxy]-34-
4

Similar Publications

Alpha-Lipoic Acid-Mediated Inhibition of LTB Synthesis Suppresses Epithelial-Mesenchymal Transition, Modulating Functional and Tumorigenic Capacities in Non-Small Cell Lung Cancer A549 Cells.

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 PDF

Targeting TRPC channels for control of arthritis-induced bone erosion.

Sci 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 PDF

Identification of a Chemical Probe for BLT2 Activation by Scaffold Hopping.

J 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 PDF

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.

View Article and Find Full Text PDF

The ETS domain-containing hematopoietic transcription factor PU.1 mediates the induction of arachidonate 5-lipoxygenase by multi-walled carbon nanotubes in macrophages in vitro.

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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!