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Updated: Jul 30, 2025
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Discovery of selective HDAC6 inhibitors based on a multi-layer virtual screening strategy
Xingang Liu1, Wenying Yan2, Songsong Wang1
1School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, China; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, China; Key Laboratory of Innovative Drug Research and Evaluation of Hebei Province, Shijiazhuang, 050017, China.
This study developed a virtual screening method to identify new histone deacetylase 6 (HDAC6) inhibitors for cancer therapy. Several compounds showed promising nanomolar activity and anti-tumor effects, offering potential for drug development.
Area of Science:
- Medicinal Chemistry
- Computational Biology
- Oncology
Background:
- Abnormal histone deacetylase 6 (HDAC6) is linked to various cancers, making it a key therapeutic target.
- Limited selective HDAC6 inhibitors are in clinical trials, necessitating urgent development of new agents.
Purpose of the Study:
- To establish an efficient multi-layer virtual screening workflow for discovering selective HDAC6 inhibitors.
- To biologically evaluate screened compounds for enzyme inhibitory and anti-proliferative activities.
- To elucidate the molecular mechanisms of selective inhibition and identify key binding residues.
Main Methods:
- A multi-layer virtual screening workflow was designed and implemented.
- Enzyme inhibition assays and anti-tumor cell proliferation experiments were conducted.
- Computational approaches were used to analyze molecular mechanisms and binding interactions.
Main Results:
- Compounds L-25, L-32, L-45, and L-81 demonstrated nanomolar HDAC6 inhibitory activity.
- These compounds exhibited anti-proliferative effects on tumor cells, with notable cytotoxicity observed for L-45 and L-81.
- Key residues on HDAC6 crucial for ligand binding were identified through computational analysis.
Conclusions:
- The developed screening scheme effectively identified potent HDAC6 inhibitors with anti-tumor potential.
- The identified compounds provide novel scaffolds for future anti-cancer drug design targeting HDAC6.
