I-Ju Leu, Julia; Murphy, Maureen E.; George, Donna L. published the artcile< Targeting ErbB3 and cellular NADPH/NADP+ abundance sensitizes cutaneous melanomas to ferroptosis inducers>, Computed Properties of 347174-05-4, the main research area is drug targeting ErbB3 NADPH NADP tachyphylaxis melanoma ferroptosis.
Melanoma is a serious health challenge. Ferroptosis is a regulated form of oxidative cell death that shows varied efficacy in melanoma. We aimed to better understand the mol. basis for this differential ferroptosis sensitivity. We find that elevated expression of ErbB3 (V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 3) associates with ferroptosis resistance and that ErbB3 knockdown sensitizes to ferroptosis inducers. ErbB3 depletion also promotes a marked reduction in the cellular ratio of GSH/GSSG (reduced/oxidized glutathione) and that of NADPH/NADP+ (reduced/oxidized NADP), together with an increase in the abundance of the lipid peroxidation product malondialdehyde (MDA). We identify several small mol. inhibitors targeting ErbB3 signaling pathways that also reduce the NADPH/NADP+ and GSH/GSSG ratios, concomitantly sensitizing the melanomas to ferroptosis activators. These findings point to a previously unrecognized role of ErbB3 in ferroptosis sensitivity and provide new insight into pathways that regulate this cell death process.
ACS Chemical Biology published new progress about Antioxidants. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Computed Properties of 347174-05-4.
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