Related Experiment Video
Updated: May 5, 2026
09:20
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
8.5K
Discovery of Novel Metalloenzyme Inhibitors Based on Property Characterization: Strategy and Application for HDAC1
Lu Zhang1,2, Yajun Yang1, Ying Yang1
1Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Molecules (Basel, Switzerland)
|March 13, 2024
Summary
A new strategy for discovering zinc-dependent metalloenzyme inhibitors was developed. This approach successfully identified novel inhibitors for histone deacetylase 1 (HDAC1), demonstrating its effectiveness in drug discovery.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Drug Discovery
Background:
- Metalloenzymes are crucial in human physiology and disease.
- Developing specific metalloenzyme inhibitors is challenging due to metal-binding fragments (MBFs).
Purpose of the Study:
- To establish a generalized drug discovery strategy for zinc-dependent metalloenzyme inhibitors (ZnMIs).
- To identify novel inhibitors for histone deacetylase 1 (HDAC1).
Main Methods:
- Characterized properties of known zinc-dependent metalloenzyme inhibitors.
- Identified 15 potential zinc(II)-binding fragments (ZnBFs).
- Defined a customized pharmacophore feature for ZnBFs and applied it to screen for HDAC1 inhibitors.
Main Results:
- A customized pharmacophore feature was successfully defined.
- Ten potential HDAC1 inhibitors were identified using the defined feature.
- Compound 9, a known potent HDAC1 inhibitor, was among the identified compounds.
Conclusions:
- The developed strategy is effective for identifying novel inhibitors of zinc-dependent metalloenzymes.
- This approach aids in overcoming challenges associated with specificity and drug-likeness in metalloenzyme inhibitor development.
