Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361301939> ?p ?o ?g. }
- W4361301939 endingPage "2394" @default.
- W4361301939 startingPage "2373" @default.
- W4361301939 abstract "The accumulation of senescent cells has an important role in the phenotypical changes observed in ageing and in many age-related pathologies. Thus, the strategies designed to prevent these effects, collectively known as senotherapies, have a strong clinical potential. Senolytics are a type of senotherapy aimed at specifically eliminating senescent cells from tissues. Several small molecule compounds with senolytic properties have already been identified, but their specificity and range of action are variable. Because of this, potential novel senolytics are being actively investigated. Given the involvement of HDACs and the PI3K pathway in senescence, we hypothesized that the dual inhibitor CUDC-907, a drug already in clinical trials for its antineoplastic effects, could have senolytic effects. Here, we show that CUDC-907 was indeed able to selectively induce apoptosis in cells driven to senesce by p53 expression, but not when senescence happened in the absence of p53. Consistent with this, CUDC-907 showed senolytic properties in different models of stress-induced senescence. Our results also indicate that the senolytic functions of CUDC-907 depend on the inhibitory effects of both HDACs and PI3K, which leads to an increase in p53 and a reduction in BH3 pro-survival proteins. Taken together, our results show that CUDC-907 has the potential to be a clinically relevant senolytic in pathological conditions in which stress-induced senescence is involved." @default.
- W4361301939 created "2023-03-31" @default.
- W4361301939 creator A5001272680 @default.
- W4361301939 creator A5004515105 @default.
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- W4361301939 creator A5029190361 @default.
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- W4361301939 creator A5058272535 @default.
- W4361301939 creator A5069638472 @default.
- W4361301939 creator A5090311573 @default.
- W4361301939 date "2023-03-28" @default.
- W4361301939 modified "2023-09-30" @default.
- W4361301939 title "Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic" @default.
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