Structure-activity relationship of novel DAPK inhibitors identified by structure-based virtual screening.

Authors :: Okamoto M
Takayama K
Shimizu T
Muroya A
Furuya T
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2010 Apr 01; Vol. 18 (7), pp. 2728-34. Date of Electronic Publication: 2010 Feb 15.
Publication Year :: 2010
Abstract: Death-associated protein kinase (DAPK) is a serine/threonine protein kinase implicated in diverse programmed cell death pathways. DAPK is a promising target protein for the treatment of ischemic diseases. We identified novel potent and selective DAPK inhibitors efficiently by structure-based virtual screening, then further developed the hit compounds. In this paper, we describe the development of the hit compounds and the structure-activity relationship studies of the DAPK inhibitors in detail, including calculation of the solvated interaction energy (SIE), and verification of selectivity using a kinase panel.<br /> (Copyright 2010 Elsevier Ltd. All rights reserved.)

Subjects :: Algorithms
Computational Biology
Computer Simulation
Death-Associated Protein Kinases
Drug Evaluation, Preclinical
Models, Molecular
Molecular Conformation
Protein Binding
Structure-Activity Relationship
Apoptosis Regulatory Proteins antagonists & inhibitors
Calcium-Calmodulin-Dependent Protein Kinases antagonists & inhibitors
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors pharmacology

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