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

Tytuł:: Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model.
Autorzy:: Oh Y; College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.
Jung H; College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.
Kim H; College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.
Baek J; College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.
Jun J; College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.
Cho H; College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.
Im D; College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.
Hah JM; College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.
Źródło:: International journal of molecular sciences [Int J Mol Sci] 2021 Apr 08; Vol. 22 (8). Date of Electronic Publication: 2021 Apr 08.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:: Chemistry Techniques, Synthetic*
Drug Design*
Molecular Docking Simulation*
Molecular Dynamics Simulation*
Quantitative Structure-Activity Relationship*
Cell Cycle Proteins/*chemistry
Protein Kinase Inhibitors/*chemistry
Protein Serine-Threonine Kinases/*chemistry
Proto-Oncogene Proteins/*chemistry
Cell Cycle Proteins/antagonists & inhibitors ; Molecular Conformation ; Protein Binding ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/pharmacology ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Proto-Oncogene Proteins/antagonists & inhibitors ; Polo-Like Kinase 1
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Grant Information:: NRF-2019M3A9A8066500 National Research Foundation of Korea; NRF-2020R1A6A1A03042854 National Research Foundation of Korea; 2020-0-01343 Artificial Intelligence Convergence Research Center
Contributed Indexing:: Keywords: hybridization; polo-like kinase 1 (PLK1); pyrazole; quantitative structure-activity relationship
Substance Nomenclature:: 0 (Cell Cycle Proteins)
0 (Protein Kinase Inhibitors)
0 (Proto-Oncogene Proteins)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
Entry Date(s):: Date Created: 20210430 Date Completed: 20210524 Latest Revision: 20231213
Update Code:: 20240104
PubMed Central ID:: PMC8068361
DOI:: 10.3390/ijms22083865
PMID:: 33917995
: Czasopismo naukowe

Pełny tekst

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)-1 H -pyrazole-3-carboxamides, and we inspected its inhibitory activities to identify novel PLK1 inhibitors with decent potency and selectivity.

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