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Updated: Jul 27, 2025

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Recent advancement of HDAC inhibitors against breast cancer
Syed Abdulla Mehmood1, Kantrol Kumar Sahu2, Sounok Sengupta3
1Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Humdard University, New Delhi, India.
Abstract:
Recent studies highlight the great potential impact of HDAC inhibitors (HDACis) in suppressing TNBC, even though clinical trials including a single HDACis demonstrated unsatisfactory outcomes against TNBC. New compounds created to achieve isoform selectivity and/or a polypharmacological HDAC strategy have also produced interesting results. The current study discusses the HDACis pharmacophoric models and the structural alterations that produced drugs with strong inhibitory effects on TNBC progression. With more than 2 million new cases reported in 2018, breast cancer-the most common cancer among women worldwide-poses a significant financial burden on an already deteriorating public health system. Due to a lack of therapies being developed for triple-negative breast cancers and the development of resistance to the current treatment options, it is imperative to plan novel therapeutics in order to bring new medications to the pipeline. Additionally, HDACs deacetylate a large number of nonhistone cellular substrates that control a variety of biological processes, such as the beginning and development of cancer. The significance of HDACs in cancer and the therapeutic potential of HDAC inhibitor. Furthermore, we also reported molecular docking study with four HDAC inhibitors and performed molecular dynamic stimulation of the best dock score compound. Among the four ligands belinostat compound showed best binding affinity with histone deacetylase protein which was -8.7 kJ/mol. It also formed five conventional hydrogen bond with Gly 841, His 669, His 670, pro 809, and His 709 amino acid residues.
Insights
Histone deacetylase inhibitors (HDACis) show promise for triple-negative breast cancer (TNBC) treatment. Belinostat demonstrated the best binding affinity to histone deacetylase protein in molecular docking studies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Triple-negative breast cancer (TNBC) lacks effective therapies, necessitating novel treatment strategies.
- Histone deacetylases (HDACs) regulate cellular processes crucial for cancer development.
- Histone deacetylase inhibitors (HDACis) are being explored for their therapeutic potential in TNBC.
Purpose of the Study:
- To discuss pharmacophoric models and structural alterations of HDACis for potent TNBC inhibition.
- To investigate the therapeutic potential of HDAC inhibitors against TNBC.
- To perform molecular docking and dynamic simulation of HDAC inhibitors.
Main Methods:
- Analysis of HDACis pharmacophoric models and structural modifications.
- Molecular docking study of four HDAC inhibitors against histone deacetylase protein.
- Molecular dynamic simulation of the best-docked compound.
Main Results:
- Belinostat exhibited the highest binding affinity (-8.7 kJ/mol) to histone deacetylase protein.
- Belinostat formed five conventional hydrogen bonds with key amino acid residues (Gly 841, His 669, His 670, Pro 809, His 709).
- Structural insights into HDAC inhibition provide a basis for developing novel TNBC therapeutics.
Conclusions:
- HDAC inhibitors, particularly belinostat, hold significant potential for TNBC treatment.
- Pharmacophore modeling and molecular simulations are valuable tools for designing effective HDACis.
- Further development of selective and polypharmacological HDAC strategies is warranted for TNBC.
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