Selective Inhibition of HDAC1 by Macrocyclic Polypeptide for the Treatment of Glioblastoma: A Binding Mechanistic Analysis Based on Molecular Dynamics.

ABSTRACT: Glioblastoma (GBM) is the most common and aggressive intracranial malignant brain tumor, and the abnormal expression of HDAC1 is closely correlated to the progression, recurrence and metastasis of GBM cells, making selective inhibition of HDAC1 a promising strategy for GBM treatments. Among all available selective HDAC1 inhibitors, the macrocyclic peptides have gained great attention due to their remarkable inhibitory selectivity on HDAC1. However, the binding mechanism underlying this selectivity is still elusive, which increases the difficulty of designing and synthesizing the macrocyclic peptide-based anti-GBM drug. Herein, multiple computational approaches were employed to explore the binding behaviors of a typical macrocyclic peptide FK228 in both HDAC1 and HDAC6. Starting from the do

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC7078330 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature