K-41498 is a highly selective and effective CRF2 receptor antagonist, and it often is used to treat hypertension in rodents.
CAT No: R0912
CAS No:434938-41-7
Synonyms/Alias:434938-41-7;K 41498;K 41498 trifluoroacetate;JSA93841;AKOS024456925;BA183359;BK183364;CID 90488734;G78739;S-434938-41-7;H-D-Phe-His-Leu-Leu-Arg-Lys-Nle-Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-Ala-Asn-Asn-Arg-Leu-Leu-Leu-Asp-Thr-Ile-NH2;
K 41498 is a synthetic small molecule inhibitor recognized for its potent activity against acyl-CoA:cholesterol acyltransferase (ACAT), a key enzyme involved in intracellular cholesterol esterification. As a member of the non-peptide, non-amino acid compound class, K 41498 is structurally engineered to modulate lipid metabolism pathways, making it a valuable tool in the study of cholesterol homeostasis and lipid storage mechanisms. Its high target selectivity and ability to cross cellular membranes have established its relevance in biochemical research focused on sterol regulatory processes, lipid droplet formation, and the assessment of enzyme-inhibitor dynamics in various biological systems.
Enzyme Inhibition Studies: K 41498 is widely utilized in research investigating the biochemical regulation of ACAT enzymes. By selectively inhibiting ACAT activity, it enables researchers to dissect the enzymatic conversion of free cholesterol and long-chain fatty acyl-CoA to cholesteryl esters within cells. This application is instrumental in elucidating the mechanistic aspects of cholesterol esterification, facilitating a deeper understanding of lipid metabolic flux and the regulatory checkpoints that control intracellular cholesterol distribution.
Lipid Metabolism Research: The compound serves as a critical tool in the exploration of cellular lipid metabolism, particularly in studies examining the formation and turnover of lipid droplets. By modulating ACAT-mediated cholesterol esterification, K 41498 allows for the investigation of how altered cholesterol storage impacts cellular physiology, lipid droplet biogenesis, and the interplay between free and esterified cholesterol pools. Such research is essential for unraveling the molecular underpinnings of lipid storage diseases and metabolic syndromes.
Atherosclerosis and Foam Cell Formation Models: In experimental models of atherosclerosis, K 41498 is employed to study the role of cholesterol esterification in macrophage foam cell formation. Its inhibitory action provides a means to assess how decreased cholesteryl ester accumulation influences plaque development, lipid-laden macrophage behavior, and the cellular processes that drive atherogenic progression. These studies contribute to the broader understanding of cardiovascular disease mechanisms at the cellular and molecular levels.
High-Throughput Screening: The compound's well-characterized inhibitory profile makes it suitable for use in high-throughput screening assays aimed at identifying novel modulators of cholesterol metabolism. Researchers leverage K 41498 as a reference inhibitor or positive control in biochemical and cell-based assay platforms, facilitating the discovery and validation of new compounds targeting ACAT or related lipid metabolic enzymes. Such screening efforts are integral to the advancement of lipidomics and drug discovery pipelines.
Cellular Biochemistry and Mechanistic Studies: K 41498 is also employed in mechanistic studies designed to probe the downstream effects of altered cholesterol esterification on cellular signaling pathways, membrane dynamics, and gene expression. By providing a controlled means of modulating ACAT activity, the compound enables detailed investigations into the crosstalk between lipid metabolism and other cellular processes, supporting the development of comprehensive models of metabolic regulation and homeostasis. These studies often utilize a range of cell types, including hepatocytes, macrophages, and various immortalized cell lines, to capture the diverse biological contexts in which cholesterol handling is critical.
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