Title:Cheminfomatic-based Drug Discovery of Human Tyrosine Kinase Inhibitors
Volume: 16
Issue: 13
Author(s): Terry-Elinor Reid, Joseph M. Fortunak, Anthony Wutoh and Xiang Simon Wang
Affiliation:
Keywords:
Cheminformatics, Ligand-based drug discovery, Quantitative structure–activity relationship, Pharmacophore modeling,
Tyrosine kinase inhibitors, Vascular endothelial growth factor, Epidermal growth factor receptor, Platelet-derived growth
factor receptor, Hepatocyte growth factor receptor.
Abstract: Receptor Tyrosine Kinases (RTKs) are essential components for regulating cell-cell signaling
and communication events in cell growth, proliferation, differentiation, survival and metabolism.
Deregulation of RTKs and their associated signaling pathways can lead to a wide variety of human
diseases such as immunodeficiency, diabetes, arterosclerosis, psoriasis and cancer. Thus RTKs have
become one of the most important drug targets families in recent decade. Pharmaceutical companies
have dedicated their research efforts towards the discovery of small-molecule inhibitors of RTKs,
many of which had been approved by the U.S. Food and Drug Administration (US FDA) or are currently in clinical trials.
The great successes in the development of small-molecule inhibitors of RTKs are largely attributed to the use of modern
cheminformatic approaches to identifying lead scaffolds. Those include the quantitative structure-activity relationship
(QSAR) modeling, as well as the structure-, and ligand-based pharmacophore modeling techniques in this case. Herein we
inspected the literature thoroughly in an effort to conduct a comparative analysis of major findings regarding the essential
structure-activity relationships (SARs)/pharmacophore features of known active RTK inhibitors, most of which were collected
from cheminformatic modeling approaches.
