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Updated: Aug 27, 2025
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Expression patterns and therapeutic implications of histone deacetylase-1 across carcinomas: a comprehensive
1Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Almajmaah, 11952, Kingdom of Saudi Arabia. b.alshehri@mu.edu.sa.
Abstract:
Histone deacetylases (HDACs) are a group of enzymes that control the expression of genes by deacetylating lysine residues on histone and nonhistone proteins. They control the expression of several proteins linked to the development and spread of cancer. Deregulation of HDAC1 has been reported across several tumors, and targeting HDAC1 with specific inhibitors has demonstrated a promising therapeutic strategy. Mocetinostat, an HDAC1 inhibitor, is yielding promising results both in vitro and in vivo studies. However, toxicities associated with Mocetinostat limit its therapeutic efficacy, so there is an urgent need to investigate novel HDAC1 inhibitors. The present study aimed to explore novel HDAC1 inhibitors and investigate the expression profile, and the prognostic and diagnostic significance of HDAC1 across pan-cancers. HDAC1 was found overexpressed across several tumors and its high expression signifies worse OS and RFS. Also, the study identified two novel HDAC1 inhibitors using an in-silico approach with high binding affinity for HDAC1 compared to Mocetinostat and formed significantly stable complexes. In conclusion, the study signifies that targeting HDAC1 is a promising therapeutic strategy, and exploring novel therapeutic agents through basic, translational design may lead to their ultimate use in cancer prevention.
Insights
Histone deacetylase 1 (HDAC1) is overexpressed in many cancers, correlating with poor outcomes. This study identifies novel HDAC1 inhibitors with potential for cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Histone deacetylases (HDACs) regulate gene expression and are implicated in cancer development.
- Histone deacetylase 1 (HDAC1) deregulation is observed in various tumors, making it a therapeutic target.
- Current HDAC1 inhibitors like Mocetinostat show promise but have associated toxicities, necessitating new drug discovery.
Purpose of the Study:
- To explore novel HDAC1 inhibitors.
- To investigate the expression profile of HDAC1 in pan-cancers.
- To determine the prognostic and diagnostic significance of HDAC1 in cancer.
Main Methods:
- In silico screening for novel HDAC1 inhibitors.
- Analysis of HDAC1 expression and its correlation with overall survival (OS) and relapse-free survival (RFS) across multiple cancer types.
- Assessment of binding affinity and complex stability for identified inhibitors.
Main Results:
- HDAC1 is overexpressed in several tumor types, with high expression linked to worse OS and RFS.
- Two novel HDAC1 inhibitors were identified via in silico methods, exhibiting higher binding affinity and stability than Mocetinostat.
- The identified inhibitors demonstrate potential as therapeutic agents against HDAC1.
Conclusions:
- Targeting HDAC1 remains a promising strategy for cancer therapy.
- The novel HDAC1 inhibitors identified offer potential for developing new anti-cancer drugs.
- Further translational research into these novel agents could advance cancer prevention and treatment.
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