Characterization of the HDAC/PI3K inhibitor CUDC-907 as a new senolytic

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“The mechanism of induction of senescent cell death by CUDC-907 remains to be fully elucidated.”

Credit: 2023 Al-Mansour et al.

“The mechanism of induction of senescent cell death by CUDC-907 remains to be fully elucidated.”

BUFFALO, NY- April 25th2023 – A new research paper is published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 15, Issue 7entitled, “Characterization of the HDAC/PI3K inhibitor CUDC-907 as a new senolytic.”

Accumulation of senescent cells has an important role in the phenotypic changes observed in aging and many age-related pathologies. Thus, strategies designed to prevent these effects, collectively known as senotherapy, have strong clinical potential.

Senolitic is a type of senotherapy aimed specifically at removing old cells from tissues. Several small molecule compounds with senolytic properties have been identified, but their specificity and range of action vary. Because of this, potential new senolytics are being actively investigated.

Given the involvement of HDAC and the PI3K pathway in senescence, the researchers Fares Al-Mansour, Abdullah Alraddadi, Buwei He, Anes Saleh, Marta Poblocka, Wael Alzahrani, Shaun Cowley, And Salvador Macip from Leicester University, Nahran University And The Open University of Catalonia hypothesized that a dual inhibitor of CUDC-907, a drug already in clinical trials for its antineoplastic effects, could have a senolytic effect.

“Here, we show that CUDC-907 is indeed able to selectively induce apoptosis in cells driven to senescence by p53 expression, but not when senescence occurs in the absence of p53.”

Consistent with this, CUDC-907 exhibits senolytic properties in various models of stress-induced aging. Their results also demonstrated that the senolytic function of CUDC-907 is dependent on the inhibitory effects of HDAC and PI3K, leading to an increase in p53 and a reduction in the pro-survival protein BH3. Taken together, their results demonstrate that CUDC-907 has the potential to be a clinically relevant senolytic in pathological conditions where stress-induced aging is involved.

“According to our results, CUDC-907 could be an attractive drug for use as a senolytic, alone or as part of a targeted approach.”

Continue Reading: DOI: https://doi.org/10.18632/aging.204616

Corresponding author: Salvador Macip

Appropriate e-mail: (email protected)

Keywords: aging, senolytic, HDAC, PI3K, CUDC-907

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About Aging-US:

Launched in 2009, Aging published papers of general interest and biological significance in all areas of research on aging and age-related diseases, including cancer—and now, with a particular focus on COVID-19 susceptibility as an age-dependent syndrome. topic in Aging goes beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g. p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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