Novel 15-lipoxygenase-1 inhibitor protects cells from RSL3-induced cell death

IF 5.9 2区 医学 Q1 CHEMISTRY, MEDICINAL European Journal of Medicinal Chemistry Pub Date : 2025-06-05 Epub Date: 2025-03-19 DOI:10.1016/j.ejmech.2025.117517
Jianqiu Zhang, Petra E. van der Wouden, Frank J. Dekker
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Abstract

Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxides. The enzyme 15-lipoxygenase-1 (15-LOX-1) plays a key role in catalyzing the formation of lipid peroxides. Therefore, inhibition of 15-LOX-1 enzyme activity holds promise to decrease the levels of lipid peroxidation. In this study, a novel potent 15-LOX-1 inhibitor, 5i, was developed and structure-activity relationships were explored. In vitro, this inhibitor inhibited lipid peroxidation and protected cells from RSL3-induced cell death. Thus, we report a potent 15-LOX-1 inhibitor, which can be used as a tool to investigate the role of 15-LOX-1.

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新型15-脂氧合酶-1抑制剂保护细胞免受rsl3诱导的细胞死亡
铁下垂是一种以脂质过氧化物积累为特征的调节细胞死亡形式。15-脂氧合酶-1 (15-LOX-1)在催化脂质过氧化物的形成中起关键作用。因此,抑制15-LOX-1酶活性有望降低脂质过氧化水平。在这项研究中,开发了一种新的有效的15-LOX-1抑制剂5i,并探索了结构-活性关系。在体外,该抑制剂抑制脂质过氧化并保护细胞免受rsl3诱导的细胞死亡。因此,我们报道了一种有效的15-LOX-1抑制剂,它可以作为研究15-LOX-1作用的工具。
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来源期刊
CiteScore
11.70
自引率
9.00%
发文量
863
审稿时长
29 days
期刊介绍: The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.
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