Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
As a class III receptor tyrosine kinase (RTK), FMS-like tyrosine kinase 3 (FLT3) is always overexpressed in many cases of acute leukemia. This paper studies the structure-based synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Encouragingly, compounds 15b, 16b, 24a, and 24c showed excellent biological activities in a low nanomolar range. In particular, compound 16b demonstrated significant inhibitory potency against FLT3-ITD (IC = 5.60 nM) and better antiproliferative activity than quizartinib against MV4-11 cell line (IC = 0.176 nM). It is indicated that compound 16b for the treatment of acute myeloid leukemia could be very promising.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2020.127525 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovery and Characterization of a Single-Component Halogenase for Phenazine Halogenation.
Org Lett
September 2025
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
Halogenated phenazines hold promise as antimicrobial and antibiofilm agents, yet are mainly accessed via chemical synthesis. Herein, we report PezW, a novel single-component flavin-dependent halogenase (FDH) that halogenates phenazine scaffolds, notably enabling enzymatic synthesis of bioactive 2-bromo-1-hydroxyphenazine () and 2,4-bromo-1-hydroxyphenazine (). Structural modeling and mutagenesis revealed key residues critical for substrate binding and catalysis.
View Article and Find Full Text PDFSIRT1 as a potential target for age-related eye diseases: mechanisms and therapeutic strategies.
Hum Cell
September 2025
Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Age-related eye diseases (AREDs) are the leading cause of visual impairment in the elderly, affecting the structure of the anterior and posterior segments of the eye, significantly reducing the quality of life of patients, and even leading to irreversible blindness. Typical AREDs include age-related cataract (ARC), dry eye disease (DED), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), the global prevalence of which continues to rise, becoming a serious public health concern. SIRT1 is an NAD + dependent deacetylase, which plays an important physiological regulatory role in ocular tissues, mainly affecting gene expression and various cellular processes by regulating the acetylation status of substrate proteins.
View Article and Find Full Text PDFAdvances and prospects of ergothioneine in the treatment of cognitive frailty.
Ann Med
December 2025
School of Acupuncture-Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Background: To review the biological functions of ergothioneine (ERGO), its correlation with plasma levels in cognitive frailty, and research progress in treating frailty and cognitive impairment, with the aim of providing a reference for ERGO application in cognitive frailty treatment.
Methods: A comprehensive review of existing literature on ERGO's chemical structure, sources, antioxidant and anti-inflammatory effects, and its role in cognitive frailty was conducted. Clinical trial data and metabolomic studies were also analyzed to understand ERGO's therapeutic potential.
Patient-Specific Regulatory Network Rewiring in Inflammatory Bowel Disease: How Genetic Polymorphisms Divert Incoming Signals and Contribute to Disease Pathogenesis.
Inflamm Bowel Dis
September 2025
Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom.
Background: Intestinal cells receive incoming signals from neighboring cells and microbial communities. Upstream signaling pathways transduce these signals to reach transcription factors (TFs) that regulate gene expression. In inflammatory bowel disease (IBD), most single nucleotide polymorphisms (SNPs) are in non-coding genomic regions containing TF binding sites.
View Article and Find Full Text PDFTargeting O-GlcNAcylated METTL3 impedes MDS/AML progression via diminishing SRSF1 mA modification.
Mol Ther
September 2025
Xi'an No. 1 Hospital, First Affiliated Hospital of Northwest University, School of Medicine, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology of Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an,
N6-methyladenosine (mA) modification, primarily regulated by methyltransferase-like protein 3 (METTL3), plays a pivotal role in RNA metabolism and leukemogenesis. However, the post-translational mechanisms governing METTL3 stability and function remain incompletely understood. Given the widespread occurrence of O-GlcNAcylation on nuclear and cytosolic proteins, we hypothesized that METTL3 might undergo O-GlcNAcylation, thereby influencing its stability and oncogenic function in myeloid malignancies.
View Article and Find Full Text PDF