更新于：2024-11-01

GPX4 x DUSP1

更新于：2024-11-01

基本信息

关联

项与 GPX4 x DUSP1 相关的药物

DUSP1/GPX4 modulators(Zhejiang Chinese Medical University)

靶点

DUSP1 x GPX4

作用机制

DUSP1 modulators [+1]

在研机构

浙江中医药大学

原研机构

浙江中医药大学

在研适应症

三阴性乳腺癌

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GPX4 x DUSP1 相关的临床结果

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100 项与 GPX4 x DUSP1 相关的转化医学

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0 项与 GPX4 x DUSP1 相关的专利（医药）

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项与 GPX4 x DUSP1 相关的文献（医药）

2024-08-08·Journal of Medicinal Chemistry

Discovery of NO Donor-Aurovertin Hybrids as Dual Ferroptosis and Apoptosis Inducers for Treating Triple Negative Breast Cancer

Article

作者: Duan, Hong-Liang ; Fang, Luo ; Zhao, Hua-Jun ; Yang, Xi ; Chen, Yi-Li ; Bao, Shu-Min ; Wu, Rui ; Zhan, Zha-Jun ; Yuan, Ling-Jie ; Xu, Li Li ; Ma, Lie-Feng

Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure-activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.

2023-11-02·Systems Biology in Reproductive Medicine

Identification of ferroptotic genes and phenotypes in idiopathic nonobstructive azoospermia

Article

作者: Peng, Tian-Wen ; Lan, Yu ; Chen, Zhi-Cong ; Ye, Xin ; An, Geng ; Wang, Mu-Ye ; Liao, Chen ; Li, Xiao-Min ; Fu, Xin

Effective treatments for nonobstructive azoospermia (NOA), which affects 1% of all men globally, are limited by undefined pathogenic mechanisms, especially in idiopathic NOA (iNOA). Here, we tried to identify the functional ferroptosis-related genes and phenotypes involved in iNOA. Differentially expressed ferroptotic genes were identified from iNOA mRNA microarray datasets by bioinformatic analyses, and these ferroptotic genes were subsequently filtered by various algorithms. Then, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic ability of the abovementioned genes for iNOA. Generally, 11 differentially expressed ferroptotic genes were downregulated, and five genes were upregulated in iNOA samples. Four genes, including DUSP1, GPX4, HSD17B11, and SLC2A8, were technically selected and determined to be potential biomarkers for iNOA. Subsequently, similar expression levels were validated at both the RNA and protein levels in the iNOA specimens. Finally, morphologic and biochemical assays were applied to define the ferroptotic phenotypes in testes. The ferroptotic features, like shrunken mitochondria with electron-dense membranes and a reduction in cristae were observed across various cell types within iNOA patients, accompanied by the overload of ferrous ions and increased lipid peroxidation production. Our findings demonstrated that these ferroptosis genes could be involved in the underlying pathogenesis mechanisms of iNOA by regulating ferroptosis and serve as potential diagnostic biomarkers. Also, the ferroptotic phenotypes were identified in iNOA patients.

2021-04-01·Cell Death & Differentiation1区 · 生物学

Cellular degradation systems in ferroptosis

1区 · 生物学

Review

作者: Tang, Daolin ; Chen, Xin ; Kroemer, Guido ; Kang, Rui ; Yu, Chunhua

In eukaryotic cells, macromolecular homeostasis requires selective degradation of damaged units by the ubiquitin-proteasome system (UPS) and autophagy. Thus, dysfunctional degradation systems contribute to multiple pathological processes. Ferroptosis is a type of iron-dependent oxidative cell death driven by lipid peroxidation. Various antioxidant systems, especially the system xc^--glutathione-GPX4 axis, play a significant role in preventing lipid peroxidation-mediated ferroptosis. The endosomal sorting complex required for transport-III (ESCRT-III)-dependent membrane fission machinery counteracts ferroptosis by repairing membrane damage. Moreover, cellular degradation systems play a dual role in regulating the ferroptotic response, depending on the cargo they degrade. The key ferroptosis repressors, such as SLC7A11 and GPX4, are degraded by the UPS. In contrast, the overactivation of selective autophagy, including ferritinophagy, lipophagy, clockophagy and chaperone-mediated autophagy, promotes ferroptotic death by degrading ferritin, lipid droplets, circadian proteins, and GPX4, respectively. Autophagy modulators (e.g., BECN1, STING1/TMEM173, CTSB, HMGB1, PEBP1, MTOR, AMPK, and DUSP1) also determine the ferroptotic response in a context-dependent manner. In this review, we provide an updated overview of the signals and mechanisms of the degradation system regulating ferroptosis, opening new horizons for disease treatment strategies.