Discovery of potent NEK2 inhibitors as potential anticancer agents using structure-based exploration of NEK2 pharmacophoric space coupled with QSAR analyses

Mohammad A Khanfar; Fahmy Banat; Shada Alabed; Saja Alqtaishat

doi:10.1007/s11030-016-9696-5

Back

Discovery of potent NEK2 inhibitors as potential anticancer agents using structure-based exploration of NEK2 pharmacophoric space coupled with QSAR analyses

Journal article

Peer reviewed

Discovery of potent NEK2 inhibitors as potential anticancer agents using structure-based exploration of NEK2 pharmacophoric space coupled with QSAR analyses

Mohammad A Khanfar, Fahmy Banat, Shada Alabed and Saja Alqtaishat

Molecular diversity, Vol.21(1), pp.187-200

01/02/2017

DOI: https://doi.org/10.1007/s11030-016-9696-5

PMID: 27599492

Abstract

Antineoplastic Agents - chemistry

Antineoplastic Agents - pharmacology

Drug Discovery

Humans

Models, Molecular

NIMA-Related Kinases - antagonists & inhibitors

NIMA-Related Kinases - chemistry

Protein Conformation

Protein Kinase Inhibitors - chemistry

Protein Kinase Inhibitors - pharmacology

Quantitative Structure-Activity Relationship

High expression of Nek2 has been detected in several types of cancer and it represents a novel target for human cancer. In the current study, structure-based pharmacophore modeling combined with multiple linear regression (MLR)-based QSAR analyses was applied to disclose the structural requirements for NEK2 inhibition. Generated pharmacophoric models were initially validated with receiver operating characteristic (ROC) curve, and optimum models were subsequently implemented in QSAR modeling with other physiochemical descriptors. QSAR-selected models were implied as 3D search filters to mine the National Cancer Institute (NCI) database for novel NEK2 inhibitors, whereas the associated QSAR model prioritized the bioactivities of captured hits for in vitro evaluation. Experimental validation identified several potent NEK2 inhibitors of novel structural scaffolds. The most potent captured hit exhibited an [Formula: see text] value of 237 nM.

Metrics

1 Record Views

See more details

Details

Title: Discovery of potent NEK2 inhibitors as potential anticancer agents using structure-based exploration of NEK2 pharmacophoric space coupled with QSAR analyses
Creators - without role: Mohammad A Khanfar - University of Jordan
Fahmy Banat - University of Jordan
Shada Alabed - University of Jordan
Saja Alqtaishat - University of Jordan
Publication Details: Molecular diversity, Vol.21(1), pp.187-200
Identifiers: 9913470608331
Academic Unit: Alfaisal University
Language: English
Resource Type: Journal article