Histone deacetylase 6 (HDAC6) contributes to cancer metastasis in several cancers, including triple-negative breast cancer (TNBC)—the most lethal form which lacks effective therapy. Although several efforts have been invested to develop selective HDAC6 inhibitors, none has been approved by the FDA, to date. Toward this goal, existing computational studies used smaller compound libraries and shorter MD simulations. Here, we conducted structure-based virtual screening of ZINC “Druglike” library containing 17,900742 compounds using Glide virtual screening protocol comprising various filters with increasing accuracy. The top 20 hits were subjected to molecular dynamics simulation, MM-GBSA binding energy calculations, and further ADMET prediction. A total of 11 diverse compounds having a pharmacophore comprising non-hydroxamic acid zinc-binding groups, heteroaromatic linker and cap groups are proposed as novel potential HDAC6 inhibitors.

Novel potential inhibitors of histone deacetylase 6 identified using structure based virtual screening and molecular dynamics simulation

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.