scholarly journals Pharmacophore Modeling and Virtual Screening Studies of Checkpoint Kinase 1 Inhibitors

2009 ◽  
Vol 57 (7) ◽  
pp. 704-709 ◽  
Author(s):  
Jin-Juan Chen ◽  
Ting-Lin Liu ◽  
Li-Jun Yang ◽  
Lin-Li Li ◽  
Yu-Quan Wei ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Pharmacophore Modeling ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1

Identification of new checkpoint kinase-1 (Chk1) inhibitors by docking, 3D-QSAR, and pharmacophore-modeling methods

2012 ◽  
Vol 90 (8) ◽  
pp. 675-692 ◽  
Author(s):  
Premlata K. Ambre ◽  
Raghuvir R. S. Pissurlenkar ◽  
Evans C. Coutinho ◽  
Radhakrishnan P. Iyer
Keyword(s):  
Hydrogen Bond ◽  
3D Qsar ◽  
Pharmacophore Modeling ◽  
Docking Studies ◽  
Hydrogen Bond Donor ◽  
Hydrogen Bond Acceptor ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1 ◽  
Qsar Models ◽  
Potential Inhibitors

Inhibition of checkpoint kinase-1 (Chk1) by small molecules is of great therapeutic interest in the field of oncology and for understanding cell-cycle regulations. This paper presents a model with elements from docking, pharmacophore mapping, the 3D-QSAR approaches CoMFA, CoMSIA and CoRIA, and virtual screening to identify novel hits against Chk1. Docking, 3D-QSAR (CoRIA, CoMFA and CoMSIA), and pharmacophore studies delineate crucial site points on the Chk1 inhibitors, which can be modified to improve activity. The docking analysis showed residues in the proximity of the ligands that are involved in ligand–receptor interactions, whereas CoRIA models were able to derive the magnitude of these interactions that impact the activity. The ligand-based 3D-QSAR methods (CoMFA and CoMSIA) highlight key areas on the molecules that are beneficial and (or) detrimental for activity. The docking studies and 3D-QSAR models are in excellent agreement in terms of binding-site interactions. The pharmacophore hypotheses validated using sensitivity, selectivity, and specificity parameters is a four-point model, characterized by a hydrogen-bond acceptor (A), hydrogen-bond donor (D), and two hydrophobes (H). This map was used to screen a database of 2.7 million druglike compounds, which were pruned to a small set of potential inhibitors by CoRIA, CoMFA, and CoMSIA models with predicted activity in the range of 8.5–10.5 log units.

scholarly journals Discovery of Novel Checkpoint Kinase 1 Inhibitors by Virtual Screening Based on Multiple Crystal Structures

2011 ◽  
Vol 51 (11) ◽  
pp. 2904-2914 ◽  
Author(s):  
Yan Li ◽  
Dong Joon Kim ◽  
Weiya Ma ◽  
Ronald A. Lubet ◽  
Ann M. Bode ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Crystal Structures ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1

Structure-based and shape-complemented pharmacophore modeling for the discovery of novel checkpoint kinase 1 inhibitors

2009 ◽  
Vol 16 (7) ◽  
pp. 1195-1204 ◽  
Author(s):  
Xiu-Mei Chen ◽  
Tao Lu ◽  
Shuai Lu ◽  
Hui-Fang Li ◽  
Hao-Liang Yuan ◽  
...  
Keyword(s):  
Pharmacophore Modeling ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1

Identification of Compounds with Nanomolar Binding Affinity for Checkpoint Kinase-1 Using Knowledge-Based Virtual Screening

2004 ◽  
Vol 47 (8) ◽  
pp. 1962-1968 ◽  
Author(s):  
Paul D. Lyne ◽  
Peter W. Kenny ◽  
David A. Cosgrove ◽  
Chun Deng ◽  
Sonya Zabludoff ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Binding Affinity ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1 ◽  
Knowledge Based

scholarly journals Novel Design Strategy for Checkpoint Kinase 2 Inhibitors Using Pharmacophore Modeling, Combinatorial Fusion, and Virtual Screening

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Chun-Yuan Lin ◽  
Yen-Ling Wang
Keyword(s):  
Virtual Screening ◽  
Design Strategy ◽  
Pharmacophore Modeling ◽  
Dna Double Strand Breaks ◽  
Checkpoint Kinase ◽  
Screening Techniques ◽  
Checkpoint Kinase 2 ◽  
Combinatorial Fusion ◽  
Potential Inhibitors ◽  
Novel Design

Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (rtest) with the value 0.816 by combining theBesttrainBesttestandFasttrainFasttestprediction results. The potential inhibitors were selected from NCI database by screening according toBesttrainBesttest+FasttrainFasttestprediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study.

Design checkpoint kinase 2 inhibitors by pharmacophore modeling and virtual screening techniques

2013 ◽  
Vol 23 (23) ◽  
pp. 6286-6291 ◽  
Author(s):  
Yen-Ling Wang ◽  
Chun-Yuan Lin ◽  
Kuei-Chung Shih ◽  
Jui-Wen Huang ◽  
Chuan-Yi Tang
Keyword(s):  
Virtual Screening ◽  
Pharmacophore Modeling ◽  
Checkpoint Kinase ◽  
Screening Techniques ◽  
Checkpoint Kinase 2

Discovery of Novel NAMPT Inhibitors Based on Pharmacophore Modeling and Virtual Screening Techniques

2015 ◽  
Vol 17 (10) ◽  
pp. 868-878 ◽  
Author(s):  
Qianying Yi ◽  
Lu Zhou ◽  
Xin Shao ◽  
Taijin Wang ◽  
Guangkai Bao ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Pharmacophore Modeling ◽  
Screening Techniques
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