Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer

Li, Yan; Li, Guangyu; Zuo, Chenwei; Wang, Xiaolin; Han, Fang; Jia, Yi; Shang, Hai; Tian, Yu

doi:10.1016/j.ejmech.2024.116367

European Journal of Medicinal Chemistry

2024

DOI: 10.1016/j.ejmech.2024.116367

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Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer

Yan Li,

Guangyu Li,

Chenwei Zuo

et al.

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Cited by 3 publications

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Phosphatidic acid directly activates mTOR and then regulates SREBP to promote ganoderic acid biosynthesis under heat stress in Ganoderma lingzhi

Liu,

Chen,

Zhang

et al. 2024

Commun Biol

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Ganoderic acids (GAs), a class of secondary metabolites produced by the traditional medicinal mushroom Ganoderma , are a group of triterpenoids with superior biological activities. Heat stress (HS) is one of the most important environmental abiotic stresses. Understanding how organisms sense temperature and integrate this information into their metabolism is important for determining how organisms adapt to climate change and for applying this knowledge to breeding. We previously reported that HS induced GA biosynthesis, and phospholipase D (PLD)-mediated phosphatidic acid (PA) was involved in HS-induced GA biosynthesis. We screened a proteome to identify the PA-binding proteins in G. lingzhi . We reported that PA directly interacted with mTOR and positively correlated with the ability of mTOR to promote GA biosynthesis under HS. The PA-activated mTOR pathway promoted the processing of the transcription factor sterol regulatory element-binding protein (SREBP) under HS, which directly activated GA biosynthesis. Our results suggest that SREBP is an intermediate of the PLD-mediated PA-interacting protein mTOR in HS-induced GA biosynthesis. Our report established the link between PLD-mediated PA production and the activation of mTOR and SREBP in the HS response and HS-induced secondary metabolism in filamentous fungi.

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Phosphatidic acid directly activates mTOR and then regulates SREBP to promote ganoderic acid biosynthesis under heat stress in Ganoderma lingzhi

Liu,

Chen,

Zhang

et al. 2024

Commun Biol

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Latest Therapeutical Approaches for Triple-Negative Breast Cancer: From Preclinical to Clinical Research

Pont,

Marqués,

Sorolla

2024

IJMS

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Triple-negative breast cancer (TNBC) represents roughly one-sixth of all breast cancer patients, but accounts for 30–40% of breast cancer deaths. Due to the lack of typical biomarkers exploited clinically for breast cancer, it remains very difficult to treat. Moreover, its intrinsic high heterogeneity and proneness to become resistant to the drugs administered makes the treatment management very challenging for oncologists. Herein, we outline the different therapies used currently for TNBC and list the ongoing clinical trials to provide an overview of the most recent TNBC therapeutic landscape. In addition, we highlight the emerging therapies in the preclinical stage that hold the most promise, such as epigenetic modulators, CRISPR, miniproteins, radioconjugates, cancer vaccines, and PROTACs. Moreover, we navigate through the existing limitations and challenges which hamper the development of new and more effective treatments for TNBC. Lastly, we point to emerging new directions that may revolutionize future therapy for TNBC.

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Research Progress on the Biological Activity of Ganoderic Acids in Ganoderma lucidum over the Last Five Years

Wang,

Shangguan

et al. 2024

Life

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Ganoderma lucidum (G. lucidum) is a traditional edible and medicinal mushroom in China. The main bioactive components in G. lucidum include triterpenoids, polysaccharides, steroids, and sterols. Ganoderic acids (GAs) are one of the most abundant triterpenoids found in G. lucidum, garnering significant attention from researchers in the fields of medicine and health care. We summarize the extensive studies on the physiological function of GAs in anti-cancer, anti-inflammatory, radiation protection, anti-aging, liver protection, anti-microbial, and neuroprotection areas, among others. This review provides a comprehensive overview of the recent advances in the bioactivities and pharmacological mechanisms of GAs, aiming to delineate the current research directions and the state of the art in this field. This analysis helps to rapidly identify new bioactivities of GAs and understand their mechanisms, leading to more effective treatments for various diseases.

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Discovery of ganoderic acid A (GAA) PROTACs as MDM2 protein degraders for the treatment of breast cancer

Cited by 3 publications

References 52 publications

Phosphatidic acid directly activates mTOR and then regulates SREBP to promote ganoderic acid biosynthesis under heat stress in Ganoderma lingzhi

Phosphatidic acid directly activates mTOR and then regulates SREBP to promote ganoderic acid biosynthesis under heat stress in Ganoderma lingzhi

Latest Therapeutical Approaches for Triple-Negative Breast Cancer: From Preclinical to Clinical Research

Research Progress on the Biological Activity of Ganoderic Acids in Ganoderma lucidum over the Last Five Years

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