Related Experiment Video
Updated: Jul 4, 2025
Direct Measurement of KDM1A Target Engagement Using Chemoprobe-based Immunoassays
Published on: June 13, 2019
Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies
Di Han1,2,3, Jiarui Lu1,2,3, Baoyi Fan1,2,3
1School of Medical Engineering, Xinxiang Medical University, Xinxiang 453003, China.
Abstract:
Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising therapeutic target for treating various cancers (such as breast cancer, liver cancer, etc.) and other diseases (blood diseases, cardiovascular diseases, etc.), owing to its observed overexpression, thereby presenting significant opportunities in drug development. Since its discovery in 2004, extensive research has been conducted on LSD1 inhibitors, with notable contributions from computational approaches. This review systematically summarizes LSD1 inhibitors investigated through computer-aided drug design (CADD) technologies since 2010, showcasing a diverse range of chemical scaffolds, including phenelzine derivatives, tranylcypromine (abbreviated as TCP or 2-PCPA) derivatives, nitrogen-containing heterocyclic (pyridine, pyrimidine, azole, thieno[3,2-b]pyrrole, indole, quinoline and benzoxazole) derivatives, natural products (including sanguinarine, phenolic compounds and resveratrol derivatives, flavonoids and other natural products) and others (including thiourea compounds, Fenoldopam and Raloxifene, (4-cyanophenyl)glycine derivatives, propargylamine and benzohydrazide derivatives and inhibitors discovered through AI techniques). Computational techniques, such as virtual screening, molecular docking and 3D-QSAR models, have played a pivotal role in elucidating the interactions between these inhibitors and LSD1. Moreover, the integration of cutting-edge technologies such as artificial intelligence holds promise in facilitating the discovery of novel LSD1 inhibitors. The comprehensive insights presented in this review aim to provide valuable information for advancing further research on LSD1 inhibitors.
Insights
Computer-aided drug design has identified diverse chemical scaffolds as inhibitors for Lysine-specific demethylase 1 (LSD1/KDM1A), a key target in cancer and other diseases.
Area of Science:
- Biochemistry and Medicinal Chemistry
- Drug Discovery and Development
Background:
- Lysine-specific demethylase 1 (LSD1/KDM1A) is overexpressed in various cancers and diseases, making it a significant therapeutic target.
- Extensive research since 2004 has focused on developing LSD1 inhibitors, with computational approaches proving increasingly valuable.
Purpose of the Study:
- To systematically review LSD1 inhibitors developed using computer-aided drug design (CADD) technologies since 2010.
- To highlight the diverse chemical scaffolds and computational methods employed in LSD1 inhibitor discovery.
Main Methods:
- Systematic literature review of CADD studies on LSD1 inhibitors published since 2010.
- Analysis of various chemical classes including heterocyclic derivatives, natural products, and AI-discovered compounds.
- Examination of computational techniques such as virtual screening, molecular docking, and 3D-QSAR.
Main Results:
- A wide array of chemical scaffolds targeting LSD1 have been identified through CADD.
- Computational methods have been crucial in understanding inhibitor-LSD1 interactions.
- Artificial intelligence is emerging as a powerful tool for novel LSD1 inhibitor discovery.
Conclusions:
- CADD has significantly advanced the identification of LSD1 inhibitors across diverse chemical structures.
- The integration of AI promises to accelerate the discovery of next-generation LSD1-targeting therapeutics.
- This review provides a comprehensive resource for future research in LSD1 inhibitor development for various diseases.
