Category: 347174-05-4

Sun, Rongli; Liu, Manman; Xu, Kai; Pu, Yunqiu; Huang, Jiawei; Liu, Jinyan; Zhang, Juan; Yin, Lihong; Pu, Yuepu published the artcile< Ferroptosis is involved in the benzene-induced hematotoxicity in mice via iron metabolism, oxidative stress and NRF2 signaling pathway>, Name: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is oxidative stress iron metabolism benzene induced hematotoxicity ferroptosis; Benzene; Ferroptosis; Hematotoxicity; Iron overload; NRF2; Redox imbalance.

Benzene is a pollutant that widely exists in the environment and in occupational workplaces. Its exposure is closely associated with hematol. disorders and even leukemia, which poses a significant threat to public health. Thus, the underlying mechanisms should be explored. In the current study, it was investigated whether ferroptosis plays a role in benzene hematopoietic toxicity and related mechanisms. Mice were s.c. injected with benzene at 150 mg/kg b.w. to establish a hematotoxicity model. Four weeks later, the mice exposed to benzene exhibited a decrease in white blood cells, red blood cells, and Hb level, as well as reduction in frequency of hematopoietic stem and progenitor cells (HS/PCs) and the colony forming abilities of CFU-G, CFU-M, CFU-GM, and CFU-GEMM. Simultaneously, apart from ferroptosis features in the mitochondrial morphol., decreased ATP and mitochondrial membrane potential, alterations in biochem. indexes and gene expression were also observed, such as increased intracellular iron and lipid peroxidation, glutathione (GSH) depletion, and reduced glutathione peroxidase (GSH-Px) level, and upregulated PTGS2. Meanwhile, markedly altered expression of SLC7A11, GPX4, GCLC, NOX1, TFRC, FTH1, and FTL hinted that redox imbalance and dysfunction of iron uptake and storage are vital to induce ferroptosis. Addnl., decreased cytoplasmic NRF2 and increased nuclear NRF2 were also found, suggesting the activation of the NRF2 pathway. More importantly, inhibition of ferroptosis with ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially relieved the hematopoietic injuries. Our findings imply that dysregulation in the system Xc-/GPX4 axis, iron metabolism, and activation of the NRF2 pathway play a crucial role in benzene-induced ferroptosis, and reveals that taking ferroptosis as a target may be a potential intervention strategy for benzene-induced hematotoxicity.

Chemico-Biological Interactions published new progress about Actins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Name: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Gao, Zhen xing; Cui, Ze long; Zhou, Min ran; Fu, Yue; Liu, Fen; Zhang, Lu; Ma, Sai; Chen, Chun yan published the artcile< The new mitochondrial uncoupler BAM15 induces ROS production for treatment of acute myeloid leukemia>, Related Products of 347174-05-4, the main research area is BAM15 anticancer agent reactive oxygen species acute myeloid leukemia; Apoptosis; BAM15; Leukemia; Primary cells; Proliferation; ROS.

Acute myeloid leukemia (AML) is a malignant proliferative disease of myeloid hematopoietic origin and cannot be treated appropriately at present. This is due to the fact that leukemia cells are not sensitive to some of the traditional chemotherapy drugs. Or some chemotherapeutic drugs are too toxic to normal cells, affecting their wide clin. application. In this study, we identified BAM15 as a novel mitochondrial uncoupling agent by screening a library of small mol. compounds that inhibit AML cell activity. BAM15 significantly inhibited proliferation and promoted apoptosis in AML cells while at the same time being less cytotoxic to normal cells. The mechanism may be related to the disturbance of the ROS production balance. In vivo investigations revealed that BAM15 effectively suppressed AML progression and prolonged the survival time of mice. In addition, we found that BAM15 can be used in combination with cytarabine to enhance its anti-cancer activity and inhibit the activity of primary cells in AML. Therefore, we identified BAM15 as a potential drug candidate for the treatment of AML.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about Acute myeloid leukemia. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Related Products of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Zhou, Jing; Sun, Caoyu; Dong, Xu; Wang, Hui published the artcile< A novel miR-338-3p/SLC1A5 axis reprograms retinal pigment epithelium to increases its resistance to high glucose-induced cell ferroptosis>, Electric Literature of 347174-05-4, the main research area is miR3383p SLC1A5 retinal pigment epithelium high glucose cell ferroptosis; Cell ferroptosis; Diabetic retinopathy; ROS; SLC1A5; miR-338-3p.

Oxidative stress-induced cell ferroptosis occurs during the pathogenesis of diabetic retinopathy (DR), but the detailed mol. mechanisms are still unclear. The present study aimed to investigate this issue. Materials and methods: The retinal pigment epithelium (RPE) was treated with high glucose (30 mM) in vitro to mimic the realistic conditions of DR progression in vivo. Cell viability was determined by MTT assay and trypan blue staining assay. Gene expressions were examined by Real-Time qPCR and Western Blot anal. FCM was used to detect cell apoptosis and ROS generation. Dual-luciferase reporter gene system assay was used to verify the targeting sites. High glucose increased reactive oxygen species (ROS) levels, promoted cell ferroptosis, and suppressed cell proliferation and viability in RPE, which were reversed by co-treating cells with both a ferroptosis inhibitor ferrostatin-1 and an ROS scavenger, N-acetyl-L-Cysteine (NAC). In addition, we screened out a miR-338-3p/ASCT2 (SLC1A5) axis that played an important role in this process. Mechanistically, miR-338-3p targeted the 3 untranslated regions (3UTR) of SLC1A5 for its inhibition and degradation, and high glucose downregulated SLC1A5 by upregulating miR-338-3p in RPE cells. Next, the miR-338-3p inhibitor and SLC1A5 overexpression vectors were delivered into the RPE cells, and the following gain- and loss-of-function experiments validated that both miR-338-3p ablation and SLC1A5 upregulation abrogated the regulating effects of high glucose on cell proliferation, viability, ferroptosis and ROS production in RPE cells. Collectively, data in the present study indicated that targeting the miR-338-3p/SLC1A5 axis could block high glucose-induced ferroptosis in RPE cells.

Journal of Molecular Histology published new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Electric Literature of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Nyakas, Marta; Fleten, Karianne Giller; Haugen, Mads Haugland; Engedal, Nikolai; Sveen, Christina; Farstad, Inger Nina; Floerenes, Vivi Ann; Prasmickaite, Lina; Maelandsmo, Gunhild Mari; Seip, Kotryna published the artcile< AXL inhibition improves BRAF-targeted treatment in melanoma>, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is BGB324 vemurafenib anticancer agent AXL BRAF proteome metastatic melanoma.

More than half of metastatic melanoma patients receiving standard therapy fail to achieve a long-term survival due to primary and/or acquired resistance. Tumor cell ability to switch from epithelial to a more aggressive mesenchymal phenotype, attributed with AXL high mol. profile in melanoma, has been recently linked to such event, limiting treatment efficacy. In the current study, we investigated the therapeutic potential of the AXL inhibitor (AXLi) BGB324 alone or in combination with the clin. relevant BRAF inhibitor (BRAFi) vemurafenib. Firstly, AXL was shown to be expressed in majority of melanoma lymph node metastases. When treated ex vivo, the largest reduction in cell viability was observed when the two drugs were combined. In addition, a therapeutic benefit of adding AXLi to the BRAF-targeted therapy was observed in pre-clin. AXL high melanoma models in vitro and in vivo. When searching for mechanistic insights, AXLi was found to potentiate BRAFi-induced apoptosis, stimulate ferroptosis and inhibit autophagy. Altogether, our findings propose AXLi as a promising treatment in combination with standard therapy to improve therapeutic outcome in metastatic melanoma.

Scientific Reports published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (BRAF). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Qin, Lu-Yun; Guan, Peng; Wang, Jian-Xin; Chen, Yu; Zhao, Ya-Shuo; Yang, Sheng-Chang; Guo, Ya-Jing; Wang, Na; Ji, En-Sheng published the artcile< Therapeutic potential of astragaloside IV against Adriamycin-induced renal damage in rats via ferroptosis>, Computed Properties of 347174-05-4, the main research area is renal damage ferroptosis astragaloside IV therapeutic potential; Adriamycin; astragaloside Ⅳ; ferroptosis; iron metabolism; kidney.

Adriamycin (ADR) has been utilized to treat cancer for several decades. However, ADR-induced renal injury is one of the most common side effects accompanying ADR therapy. In the present study, we revealed that astragaloside IV (ASIV) was beneficial for renal injury caused by Adriamycin. We demonstrated that ASIV significantly ameliorated kidney injury, improved renal dysfunction, reduced oxidative stress, alleviated iron accumulation, and inhibited the induction of ferroptosis by ADR. ASIV also rescued the intracellular levels of nuclear factor-erythroid-2-related factor 2 (Nrf2) and promoted nuclear translocation of Nrf2. These protective effects of ASIV on renal injury might be attained through the ASIV-induced activation of the Pi3K/Akt signaling pathway. In vitro, the treatment of the HK-2 cells with fer-1 or deferoxamine mesylate obviously improved cell viability during Adriamycin administration. On the other hand, the protective role of ASIV can be abrogated by RSL3 to some extent. Moreover, ASIV lowered the expression of transferrin receptor 1 and divalent metal transporter 1 while enhancing the expression of ferropotin 1 and glutathione peroxidase 4 in ADR administrated cells, the effects of which were akin to those of deferoxamine mesylate. Furthermore, ASIV increased the phosphorylation of Pi3K, Akt, and the expression of Nrf2 and glutathione peroxidase 4 compared to HK-2 cells stimulated by ADR. However, Pi3K inhibitor LY294002 abrogated these activations. In conclusion, ferroptosis may involve in ADR-induced nephrotoxicity, and ASIV might protect nephrocytes against ADR-induced ferroptosis, perhaps via activations of the Pi3K/Akt and Nrf2 signaling pathways.

Frontiers in Pharmacology published new progress about Antioxidant enzymes Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Computed Properties of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Liu, Xinliang; Qi, Kai; Gong, Yi; Long, Xiang; Zhu, Shuqiang; Lu, Feng; Lin, Kun; Xu, Jianjun published the artcile< Ferulic Acid Alleviates Myocardial Ischemia Reperfusion Injury Via Upregulating AMPKα2 Expression-Mediated Ferroptosis Depression>, Formula: C15H22N2O2, the main research area is myocardial ischemia reperfusion injury ferulic acid ferroptosis cardioprotective.

Ferroptosis, a recently discovered form of regulated cell death that is characterized by iron accumulation and excessive reactive oxygen species generation, has been favored by most researchers. Increasing evidence suggest that ferulic acid (FA) could exert marked effects to myocardial ischemia reperfusion (I/R) injury, although the understanding of its mol. mechanism is still limited. In our study, the myocardial I/R injury model was established to explore the relationship between I/R injury and ferroptosis. First, we successfully constructed myocardial I/R injury model with changes in ST segment, increased creatine phosphokinase, lactate dehydrogenase activities, and N-Terminal Pro Brain Natriuretic Peptide content, and a significantly larger infarct size. Then, the increased levels of the Ptgs2 mRNA, Fe2+ accumulation, and a decreased reduced glutathione/oxidized glutathione disulfide ratio were detected in ischemia-reperfusion-injured heart, which is highly consistent with ferroptosis. However, these effects were significantly improved after FA treatment. Based on these results, FA increased the activities of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, decreased the malondialdehyde level, ameliorated the production of reactive oxygen species, and promoted the generation of ATP. These effects of FA are similar to those of the ferroptosis inhibitor ferrostatin-1. Upregulation of AMPKα2 and Glutathione Peroxidase 4 expression were also observed in the FA group. Compound C, a specific AMP (AMP)-activated protein kinase inhibitor, significantly blocked the protective effect of FA. These findings underlined that FA inhibits ferroptosis by upregulating the expression of AMPKα2 and serves as a cardioprotective strategy.

Journal of Cardiovascular Pharmacology published new progress about Antioxidant enzymes Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Formula: C15H22N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Wang, Fengxiang; Graham, Emily T.; Naowarojna, Nathchar; Shi, Zhennan; Wang, Yuqi; Xie, Guanglei; Zhou, Lili; Salmon, Wendy; Jia, Jie-Min; Wang, Xi; Huang, Yuwei; Schreiber, Stuart L.; Zou, Yilong published the artcile< PALP: A rapid imaging technique for stratifying ferroptosis sensitivity in normal and tumor tissues in situ>, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is tumor tissues stratifying ferroptosis sensitivity PALP rapid imaging technique; cancer; ferroptosis sensitivity stratification; imaging; in situ quantitation; lipid peroxidation; polyunsaturated lipid.

Ferroptosis is an emerging cancer suppression strategy. However, how to select cancer patients for treating with ferroptosis inducers remains challenging. Here, we develop photochem. activation of membrane lipid peroxidation (PALP), which uses targeted lasers to induce localized polyunsaturated fatty acyl (PUFA)-lipid peroxidation for reporting ferroptosis sensitivity in cells and tissues. PALP captured by BODIPY-C11 can be suppressed by lipophilic antioxidants and iron chelation, and is dependent on PUFA-lipid levels. Moreover, we develop PALPv2, for studying lipid peroxidation on selected membranes along the z axis in live cells using two-photon microscopes. Using PALPv1, we detect PUFA-lipids in multiple tissues, and validate a PUFA-phospholipid reduction during muscle aging as previously reported. Patterns of PALPv1 signals across multiple cancer cell types in vitro and in vivo are concordant with their ferroptosis susceptibility and PUFA-phospholipid levels. We envision that PALP will enable rapid stratification of ferroptosis sensitivity in cancer patients and facilitate PUFA-lipid research.

Cell Chemical Biology published new progress about Antioxidants. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Cui, Jiawen; Zhou, Qin; Yu, Meijin; Liu, Yuhao; Teng, Xiaohua; Gu, Xianhong published the artcile< 4-tert-butylphenol triggers common carp hepatocytes ferroptosis via oxidative stress, iron overload, SLC7A11/GSH/GPX4 axis, and ATF4/HSPA5/GPX4 axis>, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is Cyprinus hepatocyte ferroptosis oxidative stress iron 4tertbutylphenol SLC7A11 pollution; 4-tert-butylphenol; Environmental pollutant; Ferrostatin-1; Iron homeostasis; ROS.

4-Tert-butylphenol (4-tBP) is a toxic environmental pollutant with moderate bioaccumulation, environmental persistence, and long-term toxicity. Its toxicity to aquatic organisms has become an issue of concern. However, the mol. mechanism of 4-tBP toxicity to aquatic organisms remained unclear. Liver is a target organ for environmental pollutants. Here, we established 4-tBP-exposed toxicity model in vivo and primary hepatocyte model in vitro in common carp (Cyprinus carpio L.). We found increased hepatic-somatic index (HSI) and abnormal serum biochem. indexes (ALT, AST, and LDH) after 4-tBP exposure, indicating liver damage. We further revealed that 4-tBP damaged the structural integrity of the livers with typical features of ferroptosis. Based on toxicogenomics anal., we found ferroptosis is likely to be involved in the mechanism of 4-tBP-induced liver damage. Moreover, our in vivo and in vitro experiment provided evidences that 4-tBP-exposure led to excess oxidative stress, iron overload, decreased MMP, and abnormal expression of ferroptosis-related factors. Interestingly, ferrostatin-1 (Fer-1, a ferroptosis inhibitor) pretreatment alleviated above changes. In summary, we demonstrated that 4-tBP triggered hepatocytes ferroptosis via oxidative stress, iron overload, SLC7A11/GSH/GPX4 axis, and ATF4/HSPA5/GPX4 axis. For the first time, we discovered that Fer-1 can ameliorate the toxicity of 4-tBP, which needs more investigations. Our results provided a scientific basis of mol. mechanism of 4-tBP-induced fish poisoning.

Ecotoxicology and Environmental Safety published new progress about Activating transcription factor 4 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Jiang, Hui; Zhang, Xinyu; Yang, Wanping; Li, Meiqi; Wang, Guohua; Luo, Qianqian published the artcile< Ferrostatin-1 ameliorates liver dysfunction via reducing iron in thioacetamide-induced acute liver injury in mice>, Name: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is ferrostatin1 hepatoprotective agent iron metabolism liver injury; acute liver injury; deferoxamine; ferroportin; ferroptosis inhibitor; iron; thioacetamide; transferrin receptor 1.

Hepatic iron overload always leads to oxidative stress, which has been found to be involved in the progression of liver disease. However, whether iron disorder is involved in acute liver disease and the further mol. mechanisms remain unclear. A mice model of acute liver injury (ALI) was established via i.p. injection of thioacetamide (TAA) (250 mg/kg/day) for 3 consecutive days. Ferrostatin-1 (Fer-1) was administered i.p. (2.5μM/kg/day) starting 3 days before TAA treatment. Deferoxamine (DFO) was i.p. injected (200 mg/kg/day) with TAA treatment for 3 days. We further observed the effect of Fer-1 on TAA model with high-iron diet feeding. ALI was confirmed using histol. examination and liver function activity. Moreover, expressions of iron metabolism and ferroptosis proteins were measured by Western blot anal. The study revealed that the iron accumulation and ferroptosis contributed to TAA-induced ALI pathogenesis. TAA induced prominent inflammation and vacuolar degeneration in the liver as well as liver dysfunction. In addition, protein expression of the cystine/glutamate antiporter SLC7A11 (xCT) and glutathione peroxidase 4 (GPX4) was significantly decreased in the liver, while transferrin receptor 1 (TfR1), ferroportin (Fpn) and light chain of ferritin (Ft-L) expression levels were increased after TAA exposure. As the same efficiency as DFO, pre-administration of Fer-1 significantly decreased TAA-induced alterations in the plasma ALT, AST and LDH levels compared with the TAA group. Moreover, both Fer-1 and DFO suppressed TfR1, Fpn and Ft-L protein expression and decreased iron accumulation, but did not affect xCT or GPX4 expression in the liver. Both Fer-1and DFO prevented hepatic ferroptosis by reducing the iron content in the liver. Furthermore, Fer-1 also reduced iron and reversed liver dysfunction under iron overload conditions. These findings indicate a role of TAA-induced iron accumulation and ferroptosis in the pathogenesis of ALI model. The effect of Fer-1 was consistent with that of DFO, which prevented hepatic ferroptosis by reducing the iron content in the liver. Thus, Fer-1 might be a useful reagent to reverse liver dysfunction and decreasing the iron content of the liver may be a potential therapeutic strategy for ALI.

Frontiers in Pharmacology published new progress about Cystine-glutamate transporter subunit SLC7A11 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Name: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Xuan, Yang; Wang, Huogang; Yung, Mingo Mh; Chen, Fushun; Chan, Wai-Sun; Chan, Yau-Sang; Tsui, Stephen Kw; Ngan, Hextan Ys; Chan, Karen K. L.; Chan, David W. published the artcile< SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells>, Electric Literature of 347174-05-4, the main research area is CAY10566 sc26196 cisplatin anticancer agent prognosis ferroptosis ovarian cancer; lipid desaturases; lipid metabolism; ovarian cancer; oxidative stress; peritoneal metastases.

Malignant ascites in peritoneal metastases is a lipid-enriched microenvironment and is frequently involved in the poor prognosis of epithelial ovarian cancer (EOC). However, the detailed mechanisms underlying ovarian cancer (OvCa) cells dictating their lipid metabolic activities in promoting tumor progression remain elusive. The omental conditioned medium (OCM) was established to imitate the omental or ascites microenvironment. Mass spectrometry, RT-qPCR, IHC, and western blot assays were applied to evaluate human fatty acid desaturases expressions and activities. Pharmaceutical inhibition and genetic ablation of SCD1/FADS2 were performed to observe the oncogenic capacities. RNA sequencing, lipid peroxidation, cellular iron, ROS, and Mito-Stress assays were applied to examine ferroptosis. OvCa patient-derived organoid and mouse model of peritoneal metastases were used to evaluate the combined effect of SCD1/FADS2 inhibitors with cisplatin. We found that two critical fatty acid desaturases, stearoyl-CoA desaturase-1 (SCD1) and acyl-CoA 6-desaturase (FADS2), were aberrantly upregulated, accelerating lipid metabolic activities and tumor aggressiveness of ascites-derived OvCa cells. Lipidomic anal. revealed that the elevation of unsaturated fatty acids (UFAs) was pos. associated with SCD1/FADS2 levels and the oncogenic capacities of OvCa cells. In contrast, pharmaceutical inhibition and genetic ablation of SCD1/FADS2 retarded tumor growth, cancer stem cell (CSC) formation and reduced platinum resistance. Inhibition of SCD1/FADS2 directly downregulated GPX4 and the GSH/GSSG ratio, causing disruption of the cellular/mitochondrial redox balance and subsequently, iron-mediated lipid peroxidation and mitochondrial dysfunction in ascites-derived OvCa cells. Combinational treatment with SCD1/FADS2 inhibitors and cisplatin synergistically repressed tumor cell dissemination, providing a promising chemotherapeutic strategy against EOC peritoneal metastases.

Theranostics published new progress about Antitumor agents. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Electric Literature of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics