Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model

Polo-like kinase 1 (PLK1) plays an important role in cell cycle progression and proliferation in cancer cells. PLK1 also contributes to anticancer drug resistance and is a valuable target in anticancer therapeutics. To identify additional effective PLK1 inhibitors, we performed QSAR studies of two s...

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Autores principales: Oh, Youri, Jung, Hoyong, Kim, Hyejin, Baek, Jihyun, Jun, Joonhong, Cho, Hyunwook, Im, Daseul, Hah, Jung-Mi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068361/
https://www.ncbi.nlm.nih.gov/pubmed/33917995
http://dx.doi.org/10.3390/ijms22083865
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author Oh, Youri
Jung, Hoyong
Kim, Hyejin
Baek, Jihyun
Jun, Joonhong
Cho, Hyunwook
Im, Daseul
Hah, Jung-Mi
author_facet Oh, Youri
Jung, Hoyong
Kim, Hyejin
Baek, Jihyun
Jun, Joonhong
Cho, Hyunwook
Im, Daseul
Hah, Jung-Mi
author_sort Oh, Youri
collection PubMed
description Polo-like kinase 1 (PLK1) plays an important role in cell cycle progression and proliferation in cancer cells. PLK1 also contributes to anticancer drug resistance and is a valuable target in anticancer therapeutics. To identify additional effective PLK1 inhibitors, we performed QSAR studies of two series of known PLK1 inhibitors and proposed a new structure based on a hybridized 3D-QSAR model. Given the hybridized 3D-QSAR models, we designed and synthesized 4-benzyloxy-1-(2-arylaminopyridin-4-yl)-1H-pyrazole-3-carboxamides, and we inspected its inhibitory activities to identify novel PLK1 inhibitors with decent potency and selectivity.
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spelling pubmed-80683612021-04-25 Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model Oh, Youri Jung, Hoyong Kim, Hyejin Baek, Jihyun Jun, Joonhong Cho, Hyunwook Im, Daseul Hah, Jung-Mi Int J Mol Sci Communication Polo-like kinase 1 (PLK1) plays an important role in cell cycle progression and proliferation in cancer cells. PLK1 also contributes to anticancer drug resistance and is a valuable target in anticancer therapeutics. To identify additional effective PLK1 inhibitors, we performed QSAR studies of two series of known PLK1 inhibitors and proposed a new structure based on a hybridized 3D-QSAR model. Given the hybridized 3D-QSAR models, we designed and synthesized 4-benzyloxy-1-(2-arylaminopyridin-4-yl)-1H-pyrazole-3-carboxamides, and we inspected its inhibitory activities to identify novel PLK1 inhibitors with decent potency and selectivity. MDPI 2021-04-08 /pmc/articles/PMC8068361/ /pubmed/33917995 http://dx.doi.org/10.3390/ijms22083865 Text en © 2021 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 Communication
Oh, Youri
Jung, Hoyong
Kim, Hyejin
Baek, Jihyun
Jun, Joonhong
Cho, Hyunwook
Im, Daseul
Hah, Jung-Mi
Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model
title Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model
title_full Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model
title_fullStr Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model
title_full_unstemmed Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model
title_short Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model
title_sort design and synthesis of a novel plk1 inhibitor scaffold using a hybridized 3d-qsar model
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068361/
https://www.ncbi.nlm.nih.gov/pubmed/33917995
http://dx.doi.org/10.3390/ijms22083865
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