In Silico Approach to Identify Potential Inhibitors for Axl-Gas6 Signaling

Swathik Clarancia Peter; Jayakanthan Mannu; Premendu P Mathur

doi:10.1007/978-1-4939-6740-7_17

In Silico Approach to Identify Potential Inhibitors for Axl-Gas6 Signaling

Methods Mol Biol. 2017:1549:221-229. doi: 10.1007/978-1-4939-6740-7_17.

Authors

Swathik Clarancia Peter¹, Jayakanthan Mannu¹, Premendu P Mathur²

Affiliations

¹ Department of Plant Molecular Biology and Bioinformatics, Centre for Plant Molecular Biology and Biotechnology, Tamil Nadu Agricultural University, Coimbatore, 641 003, India.
² School of Biotechnology, KIIT University, Bhubaneswar, 751024, India. ppmathur@kiit.ac.in.

PMID: 27975295
DOI: 10.1007/978-1-4939-6740-7_17

Abstract

Axl-Gas6 signaling plays an important role in numerous cancers. Axl kinase, a member of receptor tyrosine kinase family is activated by different mechanisms with Gas6 as its major activator. Targeting the Axl with inhibitors may block the binding of Gas6 and further hinders the activation of Axl. This in turn inhibits the Axl-Gas6 signaling. Thus, inhibitors of the Axl kinase may serve as ideal drug candidates for treating many human cancers. In this study we carried out virtual screening of drug-like molecules from ZINC database to identify potential inhibitors for Axl kinase. Our virtual screening study showed that ZINC83758120, ZINC34079369, and ZINC83758121 are potential drug-like lead molecules to inhibit Axl kinase.

Keywords: Axl kinase docking; Gas6 protein; QikProp Glide docking; Virtual screening; Zinc database.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Axl Receptor Tyrosine Kinase
Computer Simulation*
Databases, Protein
Drug Discovery / methods
Humans
Intercellular Signaling Peptides and Proteins / chemistry*
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism
Ligands
Models, Molecular*
Molecular Docking Simulation
Molecular Dynamics Simulation
Oncogene Proteins, Fusion / chemistry*
Oncogene Proteins, Fusion / metabolism
Protein Binding
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins / chemistry*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Receptor Protein-Tyrosine Kinases / chemistry*
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / metabolism
Signal Transduction / drug effects
Software

Substances

Antineoplastic Agents
Intercellular Signaling Peptides and Proteins
Ligands
Oncogene Proteins, Fusion
Protein Kinase Inhibitors
Proto-Oncogene Proteins
growth arrest-specific protein 6
Receptor Protein-Tyrosine Kinases
Axl Receptor Tyrosine Kinase
AXL protein, human