Phil Kyeong Heo

Bio: Phil Kyeong Heo is an academic researcher from Gyeongsang National University. The author has contributed to research in topics: Virtual screening & Pharmacophore. The author has an hindex of 1, co-authored 1 publications receiving 4 citations.

Identification of Novel Human HDAC8 Inhibitors by Pharmacophore-based Virtual Screening and Density Functional Theory Approaches

Abstract: Seokmin Kim,†,k Yuno Lee,†,k Songmi Kim,†,k Sang Jik Lee,† Phil Kyeong Heo,† Siu Kim,† Yong Jung Kwon,‡ and Keun Woo Lee†,* †Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science(RINS), Gyeongsang National University (GNU), Jinju 52828, Republic of Korea. *E-mail: kwlee@gnu.ac.kr ‡Department of Chemical Engineering, Kangwon National University, Chunchon 200-701, Republic of Korea Received August 30, 2017, Accepted December 4, 2017, Published online January 17, 2018

Histone deacetylase 8 (HDAC8) and its inhibitors with selectivity to other isoforms: An overview

Abstract: The histone deacetylases (HDACs) enzymes provided crucial role in transcriptional regulation of cells through deacetylation of nuclear histone proteins. Discoveries related to the HDAC8 enzyme activity signified the importance of HDAC8 isoform in cell proliferation, tumorigenesis, cancer, neuronal disorders, parasitic/viral infections and other epigenetic regulations. The pan-HDAC inhibitors can confront these conditions but have chances to affect epigenetic functions of other HDAC isoforms. Designing of selective HDAC8 inhibitors is a key feature to combat the pathophysiological and diseased conditions involving the HDAC8 activity. This review is concerned about the structural and positional aspects of HDAC8 in the HDAC family. It also covers the contributions of HDAC8 in the pathophysiological conditions, a preliminary discussion about the recent scenario of HDAC8 inhibitors. This review might help to deliver the structural, functional and computational information in order to identify and design potent and selective HDAC8 inhibitors for target specific treatment of diseases involving HDAC8 enzymatic activity.

An insight into selective and potent inhibition of histone deacetylase 8 through induced-fit docking, pharmacophore modeling and QSAR studies.

Abstract: Histone deacetylase 8 (HDAC8) has emerged as an important therapeutic target due to its involvement in various cancerous and neurodegenerative disease states. Since pan HDAC inhibition has been lin...

Pharmacophore-enabled virtual screening, molecular docking and molecular dynamics studies for identification of potent and selective histone deacetylase 8 inhibitors.

Abstract: Histone deacetylases (HDACs) play important roles in various biological processes, but are also notorious for their over-expression in numerous cancers and neurological disorders Therefore, the development of isoform selective HDAC inhibitors is crucial in order to prevent any side effects of pan inhibition This work focuses on identifying novel inhibitors for the selective inhibition of HDAC8, an isoform implicated in fatal diseases like T-cell lymphoma, colon cancer and childhood neuroblastoma Virtual screening of the 'In-trials' subset of ZINC database has been carried out with the help of two pharmacophore models signifying potent and selective HDAC8 inhibition A detailed molecular docking strategy, followed by molecular dynamics simulations and post-scoring with MM-GBSA calculations, has led to the identification of six promising molecules that have excellent binding with the HDAC8 active site In order to establish the selectivity profile of these molecules, their binding to off-target HDAC isoforms has also been evaluated Substitution analyses of the proposed inhibitors suggest that aromatic substituents that access the adjacent hydrophobic pocket of the HDAC8 active site have the potential to further enhance the HDAC8 selectivity

Novel Transforming Growth Factor-Beta Receptor 1 Antagonists through a Pharmacophore-Based Virtual Screening Approach

Abstract: As new drugs for the treatment of malignant tumors, transforming growth factor-beta receptor 1 (TGFβR1) antagonists have attracted wide attention. Based on the crystal structure of TGFβR1-BMS22 complex, the pharmacophore model A02 with two hydrogen bond acceptors (HBAs) and four hydrophobic (HYD) properties was constructed. From the common features of active ligands reported in the literature, pharmacophore model B10 was also generated, which has two aromatic ring centers (RAs) and two HYD properties. The two models have high sensitivity and specificity to the training set, and they are highly consistent in spatial structure. Combining the two pharmacophore models, two novel skeleton structures with potential activity were selected by virtual screening from the DruglikeDiverse, MiniMaybridge, and ZINC Drug-Like databases. Four compounds (YXY01–YXY04) with potential anti-TGFβR1 activity were designed based on the new skeleton structures. In combination with Lipinski’s rules; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and, toxicological properties predicted in the study, YXY01-03 with the novel skeleton, good drug-like properties, and potential activity were finally discovered and may have higher safety relative to BMS22, which may be valuable for further research.