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Discovery of novel dihydropteridone derivatives as orally bioavailable PLK1 inhibitors with reduced hERG inhibitory activity for acute myeloid leukemia treatment.
Eur J Med Chem
March 2025
Department of Biomedical and Chemical Engineering, Liaoning Institute of Science and Technolgy, Benxi, 117004, China. Electronic address:
Polo like kinase 1 (PLK1) is a serine/threonine kinase that plays an important role in multiple phases of the cell cycle, inhibiting its activity has been considered an effective treatment for acute myeloid leukemia (AML). Here, we reported a series of highly potent PLK1 inhibitors. Among them, compound WD6 was identified as the most promising PLK1 inhibitor, with an IC value of 0.
View Article and Find Full Text PDFAn innovative approach to development of new pyrazolylquinolin-2-one hybrids as dual EGFR and BRAF inhibitors.
Mol Divers
March 2025
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Novel quinoline-based derivatives 2a-e and 4a-j have been designed and synthesized as potential antiproliferative agents. The designed compounds were screened for their antiproliferative activity against sixty cell lines according to NCI protocol. The promising hybrids 4d-g are screened by MTT assays on three cancer cell lines: leukemia (MOLT-4), lung cancer (HOP-92), and breast cancer (T47D), with IC values ranging from 4.
View Article and Find Full Text PDFMechanism of IRF8 on osteocyte apoptosis in steroid-induced osteonecrosis of the femoral head.
Connect Tissue Res
March 2025
Department of Pediatric Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Background: Steroid-induced osteonecrosis of the femoral head (SONFH) is a metabolic disorder that leads to structural changes, collapse of the femoral head, and joint dysfunction. This study investigates the role of interferon regulatory factor 8 (IRF8) in osteocyte apoptosis in SONFH, so as to find new targets for the treatment of SONFH.
Methods: Murine long bone osteocyte-Y4 cells were cultured and treated with dexamethasone to establish SONFH cell models.
ITGAM Upregulation in Acute Myeloid Leukemia Leads to Poor Prognosis Associated With Infiltration of Inhibitory Innate Immune Cells.
Int J Lab Hematol
March 2025
Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Background: Acute myeloid leukemia (AML) is a prevalent and potentially fatal hematologic malignancy with limited improvements in survival rates over the past few decades. ITGAM, encoding CD11b, is a significant integrin component in leukocytes, involved in various biological processes. However, its role in AML prognosis and immune cell infiltration remains poorly understood.
View Article and Find Full Text PDFThe connection between 91 inflammatory cytokines and frailty mediated by 1400 metabolites: An exploratory two-step Mendelian randomization analysis.
Arch Gerontol Geriatr
February 2025
Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China. Electronic address:
Background: Frailty, a common, multifaceted, and significant geriatric condition, involves crucial roles of inflammation and metabolic factors in its onset and progression. Nevertheless, the ambiguities and complexities in earlier observational studies make current research into their interactions somewhat insufficient. Our goals were to clarify the causal link between inflammatory cytokines and frailty and to explore the potential mediating effect of metabolites using Mendelian randomization (MR) analysis.
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