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http://dx.doi.org/10.1080/14656566.2023.2259802 | DOI Listing |
J Med Chem
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery o
Aberrant activation of fibroblast growth factor receptors (FGFRs) plays a critical role in tumorigenesis across multiple cancer types, driving the development of various FGFR inhibitors. Despite clinical advances, therapeutic efficacy remains limited by the emergence of drug resistance, primarily mediated by gatekeeper mutations in FGFRs. To overcome this challenge, we designed and synthesized a novel series of 7-(1-methyl-1-indole-3-yl)-5-pyrrolo[2,3-]pyrazine derivatives as covalent pan-FGFR inhibitors targeting both wild-type and gatekeeper mutants.
View Article and Find Full Text PDFBioorg Chem
September 2025
Department of Pharmacy, Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:
RET tyrosine kinase, a key regulator of cellular signaling, is abnormally activated due to mutations or fusions in various cancers, making it an important therapeutic target. Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g.
View Article and Find Full Text PDFFront Med (Lausanne)
August 2025
Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
"Primary neuroendocrine breast carcinoma (NEBC) is an underdiagnosed subtype of breast cancer, which includes small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Accurate diagnosis remains challenging given their low incidence; misclassification as invasive breast carcinoma of no special type (IBC-NST), invasive ductal carcinoma (IDC), or a metastatic neuroendocrine carcinoma may occur. Cases with any component of adenocarcinoma and well-differentiated neuroendocrine tumors were excluded.
View Article and Find Full Text PDFInvestig Clin Urol
September 2025
Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea.
Urothelial carcinoma, the most common malignancy of the urinary tract, presents a significant challenge, particularly in its metastatic stage, where prognosis remains poor despite advancements in treatment. Historically, platinum-based chemotherapy has been the standard first-line therapy, achieving moderate response rates but limited long-term survival. Recent breakthroughs have introduced immune checkpoint inhibitors, antibody-drug conjugates (ADCs), and targeted therapies as more effective alternatives.
View Article and Find Full Text PDFPrecis Oncogenom
July 2025
Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are a class of fusion protein-driven, poor prognosis leukemias. Leukemias harboring FGFR1 fusions have previously been referred to as 8p11.2 myeloproliferative syndrome (EMS) or stem cell leukemia/lymphoma (SCLL) and are currently referred to as Myeloid/lymphoid neoplasms with FGFR1 rearrangement based on the most recent WHO classification system.
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