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http://dx.doi.org/10.1080/14789450.2020.1873134 | DOI Listing |
RSC Med Chem
August 2025
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University 4.5 Km the Ring Road Ismailia 41522 Egypt.
Protein kinases are central regulators of cell signaling and play pivotal roles in a wide array of diseases, most notably cancer and autoimmune disorders. The clinical success of kinase inhibitors-such as imatinib and osimertinib-has firmly established kinases as valuable drug targets. However, the development of selective, potent inhibitors remains challenging due to the conserved nature of the ATP-binding site, off-target effects, resistance mutations, and patient-specific variability.
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September 2025
Neuroscience and Ageing Biology Division, CSIR- Central Drug Research Institute (CDRI), Lucknow 226031, India.
The TRPA1 channel has recently emerged as a critical target for pain relief since its antagonists target the beginning of the pain transduction pathway and, thus, are devoid of side effects such as sedation, dizziness, somnolence, or cognitive impairment. Despite this clinical significance, currently, no TRPA1 inhibitors suitable for therapeutic usage exist to target these channels. Since ancient times, natural products have been known to be a rich source of new drugs, useful therapeutic agents, as well as pharmacological tools.
View Article and Find Full Text PDFESMO Open
September 2025
Sarah Cannon Research Institute United Kingdom, London, UK. Electronic address:
Background: Antibody-drug conjugates (ADCs) combine targeted monoclonal antibodies with cytotoxic payloads and are an emerging modality in systemic cancer therapy. Thirteen ADCs are Food and Drug Administration approved, with many more in development. However, design and use remain challenging, with issues including on/off-target toxicity, resistance from prior exposure to payload classes, and optimal target/payload selection.
View Article and Find Full Text PDFInvest New Drugs
September 2025
Departamento de Química and Institute for Advanced Research in Chemical Science (IAdChem), Facultad de Ciencias, Universidad Autónoma de Madrid, Módulo 13, 28049, Madrid, Spain.
The oncogenic transcription factor MYC drives proliferation, metabolism, and therapy resistance in the majority of human cancers, yet its large, nuclear protein-protein interface has long frustrated direct drug discovery. A pivotal breakthrough was the identification of Tribbles pseudokinase 3 (TRIB3) as a high-affinity scaffold that binds the helix-loop-helix/leucine zipper region of MYC, blocks the E3-ubiquitin-ligase, UBE3B, from tagging critical lysines, and thereby prolongs MYC protein half-life while enhancing MYC-MAX transcriptional output. This review integrates structural, biochemical, and in vivo data to show how genetic deletion or pharmacological eviction of TRIB3 collapses MYC levels, silences its gene program, and suppresses tumor growth in B-cell lymphomas and selected solid tumors.
View Article and Find Full Text PDFAnn Med Surg (Lond)
September 2025
University of Debrecen, Debrecen, Hungary.
Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells characterized by aberrant proliferation of myeloid lineages, driven primarily by mutations in JAK2, CALR, and myeloproliferative leukemia, leading to constitutive activation of the JAK-STAT pathway. Emerging evidence highlights mitochondrial dysfunction as a key factor in MPN pathogenesis, contributing to increased reactive oxygen species production, mitochondrial DNA mutations, and dysregulated mitochondrial dynamics, which collectively promote clonal expansion and apoptosis resistance. Targeting mitochondrial pathways has gained attention as a therapeutic strategy, with approaches including mitochondria-targeted antioxidants, metabolic inhibitors, and modulation of mitophagy and mitochondrial fission/fusion dynamics.
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