Structure-based screening of FDA-approved drugs identifies potential histone deacetylase 3 repurposed inhibitor: molecular docking and molecular dynamic simulation approaches

Histone deacetylase 3 (HDAC3) is a member of the histone deacetylase family that has emerged as a crucial target in the quest for novel therapeutic interventions against various complex diseases, including cancer. The repositioning of FDA-approved drugs presents a promising avenue for the rapid disc...

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Main Authors: Anas Shamsi (Author), Mohd Shahnawaz Khan (Author), Dharmendra Kumar Yadav (Author), Moyad Shahwan (Author)
Format: Book
Published: Frontiers Media S.A., 2024-06-01T00:00:00Z.
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100 1 0 |a Anas Shamsi  |e author 
700 1 0 |a Mohd Shahnawaz Khan  |e author 
700 1 0 |a Dharmendra Kumar Yadav  |e author 
700 1 0 |a Moyad Shahwan  |e author 
700 1 0 |a Moyad Shahwan  |e author 
245 0 0 |a Structure-based screening of FDA-approved drugs identifies potential histone deacetylase 3 repurposed inhibitor: molecular docking and molecular dynamic simulation approaches 
260 |b Frontiers Media S.A.,   |c 2024-06-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2024.1424175 
520 |a Histone deacetylase 3 (HDAC3) is a member of the histone deacetylase family that has emerged as a crucial target in the quest for novel therapeutic interventions against various complex diseases, including cancer. The repositioning of FDA-approved drugs presents a promising avenue for the rapid discovery of potential HDAC3 inhibitors. In this study, we performed a structure-based virtual screening of FDA-approved drugs obtained from DrugBank. Candidate hits were selected based on their binding affinities and interactions with HDAC3. These promising hits were then subjected to a comprehensive assessment of their biological properties and drug profiles. Our investigation identified two FDA-approved drugs, Imatinib and Carpipramine, characterized by their exceptional affinity and specificity for the binding pocket of HDAC3. These molecules demonstrated a strong preference for HDAC3 binding site and formed interactions with functionally significant residues within the active site pocket. To gain deeper insights into the binding dynamics, structural stability, and interaction mechanisms, we performed molecular dynamics (MD) simulations spanning 300 nanoseconds (ns). The results of MD simulations indicated that Imatinib and Carpipramine stabilized the structure of HDAC3 and induced fewer conformational changes. Taken together, the findings from this study suggest that Imatinib and Carpipramine may offer significant therapeutic potential for treating complex diseases, especially cancer. 
546 |a EN 
690 |a histone deacetylase 3 
690 |a FDA approved drugs 
690 |a imatinib 
690 |a carpipramine 
690 |a virtual screening 
690 |a molecular dynamic (MD) simulations 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
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786 0 |n Frontiers in Pharmacology, Vol 15 (2024) 
787 0 |n https://www.frontiersin.org/articles/10.3389/fphar.2024.1424175/full 
787 0 |n https://doaj.org/toc/1663-9812 
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