Preprint Article Version 1 This version is not peer-reviewed

Characterization of Small Molecules Inhibiting Pro-Angiogenic Activity of the Zinc Finger Transcription Factor Vezf1

Version 1 : Received: 14 May 2018 / Approved: 15 May 2018 / Online: 15 May 2018 (08:08:15 CEST)

A peer-reviewed article of this Preprint also exists.

He, M.; Yang, Q.; Norvil, A.B.; Sherris, D.; Gowher, H. Characterization of Small Molecules Inhibiting the Pro-Angiogenic Activity of the Zinc Finger Transcription Factor Vezf1. Molecules 2018, 23, 1615. He, M.; Yang, Q.; Norvil, A.B.; Sherris, D.; Gowher, H. Characterization of Small Molecules Inhibiting the Pro-Angiogenic Activity of the Zinc Finger Transcription Factor Vezf1. Molecules 2018, 23, 1615.

Journal reference: Molecules 2018, 23, 1615
DOI: 10.3390/molecules23071615

Abstract

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of angiogenic therapies that treat diseases ranging from cardiovascular to cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20uM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases raging from wound healing to cancer.

Subject Areas

Vezf1; angiogenesis; vascular biology; endothelial cells; MSS31, tube formation, small molecule inhibitors computational modeling.

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.