Epigenetics-targeted drugs: current paradigms and future challenges

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Язык: Английский

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YTHDF3-mediated FLCN/cPLA2 axis improves cardiac fibrosis via suppressing lysosomal function

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Язык: Английский

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RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Сен. 28, 2024

Язык: Английский

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Therapeutic Potential of FTO Demethylase in Metabolism and Disease Pathways

The Protein Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 9, 2025

Язык: Английский

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Pharmacology of Epitranscriptomic Modifications: Decoding the Therapeutic Potential of RNA Modifications in Drug Resistance

European Journal of Pharmacology, Год журнала: 2025, Номер 994, С. 177397 - 177397

Опубликована: Фев. 18, 2025

Язык: Английский

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The Role of M6A Modification in Autoimmunity: Emerging Mechanisms and Therapeutic Implications

Clinical Reviews in Allergy & Immunology, Год журнала: 2025, Номер 68(1)

Опубликована: Март 14, 2025

Язык: Английский

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RNA modifications in female reproductive physiology and disease: emerging roles and clinical implications

Human Reproduction Update, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Abstract BACKGROUND RNA modifications, collectively known as the epitranscriptome, represent third layer of gene regulation, influencing expression at transcriptional, post-transcriptional, and translational levels. RNA-modifying proteins (RMPs), including writers, erasers, readers, are responsible for depositing, removing, recognizing chemical modifications on molecules. These play a crucial role in linking molecular processes to cellular functions. Over past few decades, growing body laboratory evidence, alongside advances sequencing technologies, has uncovered connections between aberrant reproductive disorders, highlighting their emerging roles female fertility. Given rapid expansion epitranscriptomic research reproduction, comprehensive review is needed summarize broader impacts various rather than focusing individual alone. OBJECTIVE AND RATIONALE This aims elucidate progress understanding biology how dysregulations contribute infertility-related conditions, such polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis. Special focus will be given coding RNAs, particularly those linked fertility supported by solid evidence. The ultimate objective explore targeting RNA-modification machinery can lead development novel therapeutic interventions restoring SEARCH METHODS We conducted thorough peer-reviewed original articles reviews published over two decades using PubMed search engine. Keywords included terms related ‘N6-methyladenosine (m6A)’, ‘N4-acetylcytidine (ac4C)’, ‘adenosine-to-inosine (A–I) editing’, combined with ‘ovary’, ‘oocyte’, ‘embryo’. Additional relevant phrases were also utilized ensure coverage topic. OUTCOMES modification emerged transformative area biology, our epitranscriptome rapidly due significant high-throughput technologies. Regulatory correct deposition functional implementation modifications. Knockout animal models have identified broad, though still incomplete, list involved mammalian processes. include prevalent mRNA, m6A, well A–I editing, and, lesser extent, 5-methylcytosine (m5C) ac4C. regulatory mechanisms impact functions, folliculogenesis, oocyte maturation, fertilization, embryo development. Dysregulation may exacerbate POI, PCOS, Although clinical investigations early stages, show great promise diagnostic biomarkers targets, potential improve health outcomes. WIDER IMPLICATIONS explores relatively underexamined offering significantly advance biology. It underscores relevance disorders identifies biomarkers, RMP-targeted therapies, that could shape future decision-making personalized treatments. insights clinicians embryologists, presenting new avenues diagnosis medicine. REGISTRATION NUMBER N/A.

Язык: Английский

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Role of N6‐methyladenosine RNA modification in cancer

MedComm, Год журнала: 2024, Номер 5(9)

Опубликована: Сен. 1, 2024

Abstract N6‐methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A pivotal diverse diseases especially cancer. corelates with initiation, progression, resistance, invasion, and metastasis However, despite these insights, a comprehensive understanding its specific roles mechanisms within complex landscape cancer still elusive. This review begins by outlining key regulatory proteins their posttranslational modifications (PTMs), as well role chromatin accessibility transcriptional activity Additionally, it highlights impact progression modulating programmed cell death affecting tumor microenvironment through various cancer‐associated immune Furthermore, discusses how microorganisms can induce enduring epigenetic changes oncogenic effect microorganism‐associated cancers altering modifications. Last, delves into immunotherapy, encompassing therapy, checkpoint blockade, cytokine adoptive transfer direct targeting regulators. Overall, this clarifies multifaceted explores targeted therapies aimed at manipulating modification, aiming to advance research improve patient outcomes.

Язык: Английский

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FTO in oral diseases: Functions, mechanisms, and therapeutic potential

The FASEB Journal, Год журнала: 2024, Номер 38(20)

Опубликована: Окт. 22, 2024

Abstract Fat mass and obesity‐associated protein (FTO) is the first identified N 6 ‐methyladenosine (m A) demethylase widely distributed in various tissues adults children. It plays an essential role diverse mRNA‐associated processes including transcriptional stability, selective splicing, mRNA translocation, also translation. Recently, emerging studies have shown that FTO involved genesis development of oral diseases. However, correlation between diseases its specific regulatory mechanism still needs further study. In this review, we will summarize discovery, distribution, gene expression, structure, biological functions, inhibitors, quantifying methods FTO, as well Notably, genetic variants are strongly associated with periodontal (PDs), temporomandibular joint osteoarthritis (TMJOA), obstructive sleep apnea (OSA). Besides, latest describe relationship PDs, head neck squamous cell carcinoma (HNSCCs), TMJOA, OSA be discussed. We elaborate on roles HNSCCs, which modulated through proliferation, migration, apoptosis, bone metabolism, immune response. The review enrich our understanding RNA epigenetic modifications present a solid theoretical foundation for to serve novel diagnosis prognostic biomarker

Язык: Английский

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Combating cancer stem cells: RNA m6A methylation and small-molecule drug discovery

Frontiers in Drug Discovery, Год журнала: 2024, Номер 4

Опубликована: Сен. 30, 2024

Cancer stem cells (CSCs) are a small population of less differentiated with robust self-renewal ability. CSCs have been recognized as the root cause tumor initiation, progression, relapse, and drug resistance. Recent studies from us others highlighted that N 6 -methyladenosine (m A), most prevalent modification in mRNA, plays crucial role carcinogenesis CSC homeostasis. Dysregulation m A machinery has implicated survival self-renewal, thereby regulating cancer progression therapeutic In this review, we provide an overview roles molecular mechanisms RNA self-renewal. Additionally, summarize currently known small-molecule inhibitors targeting dysregulated discuss proof-of-concept focusing on efficacy these compounds eliminating cancers.

Язык: Английский

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