Work

In silico exploration natural compounds for the discovery of novel DNMT3A inhibitors as potential therapeutic agents for acute myeloid leukemia

Year: 2025

Type: article

Abstract: ABSTRACT Aberrant DNA methylation, a hallmark of acute myeloid leukemia (AML), is catalyzed by DNA methyltransferase 3A (DNMT3A). Approximately 20-30% of AML patients harbor DNMT3A mutations, leading to disrupted DNA methylation patterns and leukemogenesis. To identify potential therapeutic interventions, this study employed computational drug discovery. A pharmacophore model was constructed and utilized to screen a natural product database, yielding a set of promising compounds. Subsequent molecular docking, MM-GBSA calculations, and ADMET profiling identified two compounds, CNP0375130 and CNP0256178, as potential DNMT3A inhibitors. These compounds exhibited favorable binding affinities and demonstrated desirable drug-like properties. Molecular dynamics simulations confirmed stable protein-ligand interactions. These findings suggest that CNP0375130 and CNP0256178 may serve as promising lead compounds for the development of novel anti-leukemic therapies targeting DNMT3A, and contribute to the ongoing efforts to develop targeted therapies for leukemia.

Source: In Silico Research in Biomedicine

DOI: 10.1016/j.insi.2025.100006

Authors: Uddalak Das, Akshay Uttarkar, Jitendra Kumar, Vidya Niranjan

Institutions: Jawaharlal Nehru University, University of Agricultural Sciences, Bangalore, R.V. College of Engineering, Visvesvaraya Technological University, Biotechnology Industry Research Assistance Council

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Drug Discovery

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,000