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Discovery, Optimization, and Preclinical Pharmacology of EP652, a METTL3 Inhibitor with Efficacy in Liquid and Solid Tumor Models.
J Med Chem
January 2025
Epics Therapeutics SA, rue Adrienne Bolland 47, Gosselies 6041, Belgium.
METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.
View Article and Find Full Text PDFEvaluation of the practical application of the category-imbalanced myeloid cell classification model.
PLoS One
January 2025
School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China.
The incidence of acute myeloid leukemia (AML) is increasing annually, and timely diagnostic and treatments can substantially improve patient survival rates. AML typing traditionally relies on manual microscopy for classifying and counting myeloid cells, which is time-consuming, laborious, and subjective. Therefore, developing a reliable automated model for myeloid cell classification is imperative.
View Article and Find Full Text PDFInotuzumab ozogamicin (InO) is approved for treatment of relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Previous studies reported higher rates of post- hematopoietic stem cell transplant (HSCT) hepatic sinusoidal obstruction syndrome (SOS) in patients receiving InO versus chemotherapy prior to HSCT. It is unknown if a lower InO dose would reduce risk of post-HSCT SOS or if it would impact efficacy.
View Article and Find Full Text PDFRedox biomarker levels in patients with myelodysplastic syndrome.
Biomed Rep
March 2025
Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, Larissa 41500, Greece.
Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder characterized by insufficient hematopoiesis, peripheral blood cytopenia and an increased risk for malignant transformation to acute myeloid leukemia. Several factors, such as age, sex and lifestyle, promote the development of MDS syndrome. Oxidative stress, along with its detrimental effects, cause hematological disorders; however, its role in the pathogenesis of MDS is unknown.
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