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Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II

Hexokinase-II (HK-II), the rate-limiting step enzyme in the glycolysis pathway, expresses high levels of cancer cells compared with normal cells. Due to its pivotal role in the different aspects of cancer physiology including cellular proliferation, metastasis, and apoptosis, HK-II provides a new th...

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Detalles Bibliográficos
Autores principales: Liu, Ruijuan, Liu, Xuewei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658052/
https://www.ncbi.nlm.nih.gov/pubmed/36364382
http://dx.doi.org/10.3390/molecules27217555
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author Liu, Ruijuan
Liu, Xuewei
author_facet Liu, Ruijuan
Liu, Xuewei
author_sort Liu, Ruijuan
collection PubMed
description Hexokinase-II (HK-II), the rate-limiting step enzyme in the glycolysis pathway, expresses high levels of cancer cells compared with normal cells. Due to its pivotal role in the different aspects of cancer physiology including cellular proliferation, metastasis, and apoptosis, HK-II provides a new therapeutic target for cancer therapy. The structure-based virtual screening targeting HK-II was used to hit identifications from small molecule databases, and the select compounds were further evaluated in biological assays. Forty-seven compounds with the lowest binding energies were identified as potential HK-II inhibitors. Among them, nine compounds displayed the highest cytotoxicity to three different cancer cells. Based on the mechanism study, compounds 4244-3659 and K611-0094 showed an obvious inhibitory effect on the HK-II enzyme. This study identified two potential inhibitors of HK-II and can be helpful for developing potential drugs targeting HK-II in tumor therapy.
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spelling pubmed-96580522022-11-15 Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II Liu, Ruijuan Liu, Xuewei Molecules Article Hexokinase-II (HK-II), the rate-limiting step enzyme in the glycolysis pathway, expresses high levels of cancer cells compared with normal cells. Due to its pivotal role in the different aspects of cancer physiology including cellular proliferation, metastasis, and apoptosis, HK-II provides a new therapeutic target for cancer therapy. The structure-based virtual screening targeting HK-II was used to hit identifications from small molecule databases, and the select compounds were further evaluated in biological assays. Forty-seven compounds with the lowest binding energies were identified as potential HK-II inhibitors. Among them, nine compounds displayed the highest cytotoxicity to three different cancer cells. Based on the mechanism study, compounds 4244-3659 and K611-0094 showed an obvious inhibitory effect on the HK-II enzyme. This study identified two potential inhibitors of HK-II and can be helpful for developing potential drugs targeting HK-II in tumor therapy. MDPI 2022-11-04 /pmc/articles/PMC9658052/ /pubmed/36364382 http://dx.doi.org/10.3390/molecules27217555 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Ruijuan
Liu, Xuewei
Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II
title Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II
title_full Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II
title_fullStr Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II
title_full_unstemmed Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II
title_short Virtual Screening and Biological Activity Evaluation of New Potent Inhibitors Targeting Hexokinase-II
title_sort virtual screening and biological activity evaluation of new potent inhibitors targeting hexokinase-ii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658052/
https://www.ncbi.nlm.nih.gov/pubmed/36364382
http://dx.doi.org/10.3390/molecules27217555
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