Next Article in Journal
Hybrid Molecules Composed of 2,4-Diamino-1,3,5-triazines and 2-Imino-Coumarins and Coumarins. Synthesis and Cytotoxic Properties
Next Article in Special Issue
Development of Thiophene Compounds as Potent Chemotherapies for the Treatment of Cutaneous Leishmaniasis Caused by Leishmania major
Previous Article in Journal
Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression
Previous Article in Special Issue
The Mechanism for siRNA Transmembrane Assisted by PMAL
Open AccessArticle

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

1
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA
2
Department of Anesthesiology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA
3
GenAdam Therapeutics, Inc., 37 Neillian Crescent, Jamaica Plain, MA 02130, USA
4
Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(7), 1615; https://doi.org/10.3390/molecules23071615
Received: 14 May 2018 / Revised: 23 June 2018 / Accepted: 24 June 2018 / Published: 3 July 2018
(This article belongs to the Special Issue Directed Drug Design and Molecular Therapy)
Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of anti-angiogenic therapies that treat various diseases, including 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 20 μM. 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. View Full-Text
Keywords: Vezf1; angiogenesis; vascular biology; endothelial cells; MSS31; tube formation; small molecule inhibitors computational modeling Vezf1; angiogenesis; vascular biology; endothelial cells; MSS31; tube formation; small molecule inhibitors computational modeling
Show Figures

Figure 1

MDPI and ACS Style

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop