Rational design and development of HDAC ...
Document type :
Article dans une revue scientifique
Permalink :
Title :
Rational design and development of HDAC inhibitors for breast cancer treatment
Author(s) :
Mody, Deepansh [Auteur]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Savvides, Savvas N. [Auteur]
Gupta, Vibha [Auteur]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Savvides, Savvas N. [Auteur]
Gupta, Vibha [Auteur]
Journal title :
Current Pharmaceutical Design
Abbreviated title :
CPD
Publisher :
Bentham Science Publishers Ltd.
Publication date :
2021-09-17
ISSN :
1381-6128
English keyword(s) :
Histone deacetylases
HDACi
rational drug discovery
structural insights
breast cancer
differential HDAC expression
HDAC-isoform selectivity
HDACi
rational drug discovery
structural insights
breast cancer
differential HDAC expression
HDAC-isoform selectivity
HAL domain(s) :
Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique
Chimie/Chimie théorique et/ou physique
English abstract : [en]
Background:
Breast cancer is the most prevalent cancer amongst females across the globe and with over 2 million new cases reported in 2018, it poses huge economic burden to the already dwindling public health. A ...
Show more >Background: Breast cancer is the most prevalent cancer amongst females across the globe and with over 2 million new cases reported in 2018, it poses huge economic burden to the already dwindling public health. A dearth of therapies in the pipeline to treat triple-negative breast cancers, and acquisition of resistance against existing line of treatments urges the need to strategize novel therapeutics in order to add new drugs to the pipeline. HDAC inhibitors (HDACi) is one such class of small molecule inhibitors that target histone deacetylases to bring about chromosomal remodelling and normalize dysregulated gene expression that marks breast cancer progression. Objective: While four HDACi have been approved by the FDA for treatment of different cancer types, no HDACi is specifically earmarked for clinical management of breast cancer. Owing to the differential HDAC expression pertaining to different types of breast cancers, isoform-selective HDAC inhibitors need to be discovered. Conclusion: This review attempts to set the stage for rational structure-based discovery of isoform-selective HDACi by providing structural insights into different HDACs and their catalytic folds based on their classes and individual landscape. Development of inhibitors in accordance with the differential expression of HDAC isoforms exhibited in breast cancer cells is a promising strategy to rationally design selective and effective inhibitors, adopting a ‘personalized-medicine’ approach.Show less >
Show more >Background: Breast cancer is the most prevalent cancer amongst females across the globe and with over 2 million new cases reported in 2018, it poses huge economic burden to the already dwindling public health. A dearth of therapies in the pipeline to treat triple-negative breast cancers, and acquisition of resistance against existing line of treatments urges the need to strategize novel therapeutics in order to add new drugs to the pipeline. HDAC inhibitors (HDACi) is one such class of small molecule inhibitors that target histone deacetylases to bring about chromosomal remodelling and normalize dysregulated gene expression that marks breast cancer progression. Objective: While four HDACi have been approved by the FDA for treatment of different cancer types, no HDACi is specifically earmarked for clinical management of breast cancer. Owing to the differential HDAC expression pertaining to different types of breast cancers, isoform-selective HDAC inhibitors need to be discovered. Conclusion: This review attempts to set the stage for rational structure-based discovery of isoform-selective HDACi by providing structural insights into different HDACs and their catalytic folds based on their classes and individual landscape. Development of inhibitors in accordance with the differential expression of HDAC isoforms exhibited in breast cancer cells is a promising strategy to rationally design selective and effective inhibitors, adopting a ‘personalized-medicine’ approach.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CNRS
CNRS
Research team(s) :
Computational Molecular Systems Biology
Submission date :
2021-10-14T14:28:02Z
2021-10-18T08:06:26Z
2022-10-21T14:59:28Z
2021-10-18T08:06:26Z
2022-10-21T14:59:28Z
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