Discovery of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) Inhibitors by Ligand-based Virtual High Throughput Screening.

Molecular Informatics
Chelliah SelvamRamasamy Thilagavathi

Abstract

Virtual screening has become one of the important tools in the discovery of novel hits for the given target. The present study reports the successful application of ligand-based virtual screening method for the discovery of novel vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. We generated a ligand query model with pharmacophore features from the reported VEGFR-2 inhibitors using vROCS tool and performed virtual screening. Among the 2.4 million lead like molecules of ZINC database screened, nineteen prioritized compounds were purchased from Enamine and ChemBridge and tested for VEGFR-2 inhibitory activity using Promega's ADP-Glo™ kinase assay. Experimental validation led to the discovery of four compounds 3, 7, 10, and 13. Compound 10 exhibited moderate inhibitory activity with the IC50 value of 19.3 μM. Molecular docking was performed for these compounds and the predicted binding modes reported in this paper may further guide to explore the possible structural changes to get more potent VEGFR-2 inhibitors.

References

Jan 16, 2002·Drug Discovery Today·Gisbert Schneider, Hans-Joachim Böhm
Feb 13, 2003·Biopolymers·Mark R McGannFrank K Brown
Dec 17, 2004·Nature·Brian K Shoichet
Mar 4, 2005·Journal of Medicinal Chemistry·Thomas S RushAnthony Nicholls
Dec 6, 2005·Journal of Computer-aided Molecular Design·Anthony Nicholls, J Andrew Grant
Jun 27, 2007·Journal of Chemical Information and Modeling·Georgia B McGaugheyWendy D Cornell
Mar 12, 2010·Journal of Medicinal Chemistry·Chelliah SelvamFrancine C Acher
Feb 18, 2011·Journal of Chemical Information and Modeling·Mark McGann
Apr 11, 2012·Journal of Chemical Information and Modeling·Adel HamzaChang-Guo Zhan
Oct 23, 2012·Journal of Chemical Information and Modeling·Paul C D Hawkins, Anthony Nicholls
Oct 27, 2012·Journal of Medicinal Chemistry·Francesca MusumeciSilvia Schenone
Sep 4, 2015·Bioorganic & Medicinal Chemistry Letters·Thilagavathi Ramasamy, Chelliah Selvam
Jan 23, 2016·Cancer Letters·Giandomenico RovielloDaniele Generali
Jun 12, 2019·CA: a Cancer Journal for Clinicians·Kimberly D MillerRebecca L Siegel

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.