Investigating the binding mechanism of AML inhibitors based on panobinostat with HDAC3 proteins using Gaussian accelerated molecular dynamics.

ABSTRACT: Class I histone deacetylases (HDACs) play a crucial role in the transformation and survival of myeloid and lymphoid malignancies, with HDAC1, 2, and 3 (Class I HDACs) being potential molecular targets for acute myelogenous leukemia (AML) treatment. Among them, HDAC3 depletion or inhibition significantly reduces proliferation and promotes differentiation in leukemia, with inhibitors like Panobinostat and compound 13a showing promise in suppressing its activity. In this study, we utilized Gaussian accelerated molecular dynamics (GaMD) simulations to compare the inhibitory potency of 13a and Panobinostat against HDAC3. Our findings suggest that the superior inhibitory activity of 13a may be attributed to its stronger interactions with HDAC3. Distance analysis demonstrated that 13a maintains a

SUBMITTER: Yu X 

PROVIDER: S-EPMC12284631 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature