title: SAHA-based novel HDAC inhibitor design by core hopping method.
abstract: The catalytic activity of the histone deacetylase (HDAC) is directly relevant to the pathogenesis of cancer, and HDAC inhibitors represented a promising strategy for cancer therapy. SAHA (suberoanilide hydroxamic acid), an effective HDAC inhibitor, is an anti-cancer agent against T-cell lymphoma. However, SAHA has adverse effects such as poor pharmacokinetic properties and severe toxicities in clinical use. In order to identify better HDAC inhibitors, a compound database was established by core hopping of SAHA, which was then docked into HDAC-8 (PDB ID: 1T69) active site to select a number of candidates with higher docking score and better interaction with catalytic zinc ion. Further ADMET prediction was done to give ten compounds. Molecular dynamics simulation of the representative compound 101 was performed to study the stability of HDAC8-inhibitor system. This work provided an approach to design novel high-efficiency HDAC inhibitors with better ADMET properties.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lan-Lan
authors.initials: LL
authors.lastname: Zang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Xu
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xian-Bin
authors.initials: XB
authors.lastname: Xie
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Electronic address: chengxianchao@aliyun.com.
authors.forename: Xian-Chao
authors.initials: XC
authors.lastname: Cheng
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ma
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Electronic address: wangrunling@tijmu.edu.cn.
authors.forename: Run-Ling
authors.initials: RL
authors.lastname: Wang
mesh_terms: D056572:Histone Deacetylase Inhibitors / Q000737:chemistry*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D016399:Lymphoma, T-Cell; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids
keywords: ADMET; Core hopping; Docking; Molecular dynamics simulation; SAHA