Abstract
Focal adhesion kinase (FAK) is a tyrosine kinase that functions as a key orchestrator of signals leading to invasion and metastasis. In the current study, the multicomplex-based pharmacophore (MCBP)-guided method has been suggested to generate a comprehensive pharmacophore of FAK kinase based on seven crystal structures of FAK-inhibitor complexes. In this investigation, a hybrid protocol of virtual screening methods, comprising of pharmacophore model-based virtual screening (PB-VS) and docking-based virtual screening (DB-VS), is used for retrieving new FAK inhibitors from commercially available chemical databases. This hybrid virtual screening approach was then applied to screen several chemical databases, including the Specs (202,408 compounds) database. Thirty-five compounds were selected from the final hits and should be shifted to experimental studies. These results may provide important information for further research of novel FAK inhibitors.
Highlights
Focal adhesion kinase (FAK) is a 125-kDa non-receptor protein tyrosine kinase that was first identified in Src-transformed fibroblasts [1]
It has been validated that the multicomplex-based pharmacophore model was capable of predicting the bioactive conformations and molecular alignments of a wide variety of FAK inhibitors in the structurally diverse datasets
The multicomplex-based pharmacophore-guided virtual screening can be used for further discovery and to design more potent FAK inhibitors and to evaluate the newly engineered compounds in de novo design
Summary
Focal adhesion kinase (FAK) is a 125-kDa non-receptor protein tyrosine kinase that was first identified in Src-transformed fibroblasts [1]. It is known that FAK is activated from integrin and growth factor receptors by auto-phosphorylation at Tyr397 [2], followed by subsequent activation of other functional phosphorylation sites to advance the signals to downstream pathways, such as AKT [3,4,5]. Based on these facts, FAK is thought to play a critical role in malignant behavior including proliferation, survival, and invasion [6,7]. FAK represents an important target for the development of anti-neoplastic and anti-metastatic drugs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
