In silico Exploration Natural Compounds for the Discovery of Novel DNMT3A Inhibitors as Potential Therapeutic Agents for Acute Myeloid Leukemia DOI Creative Commons
Uddalak Das, Akshay Uttarkar, Jitendra Kumar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 29, 2024

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

Язык: Английский

Exploring Epigenetic Complexity in Regulation of Hematopoietic Stem Cells Niche: A Mechanistic Journey from Normal to Malignant Hematopoiesis DOI

Nur Afizah Yusoff,

Zariyantey Abd Hamid,

Izatus Shima Taib

и другие.

Advances in experimental medicine and biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
In silico exploration natural compounds for the discovery of novel dnmt3a inhibitors as potential therapeutic agents for acute myeloid leukaemia DOI Creative Commons
Uddalak Das, Akshay Uttarkar, Jitendra Kumar

и другие.

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
In silico Exploration Natural Compounds for the Discovery of Novel DNMT3A Inhibitors as Potential Therapeutic Agents for Acute Myeloid Leukemia DOI Creative Commons
Uddalak Das, Akshay Uttarkar, Jitendra Kumar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 29, 2024

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

Язык: Английский

Процитировано

0