Identification of inhibitors for vascular endothelial growth factor receptor by using dynamic combinatorial chemistry

Zhao Yang; Zheng Fang; Wei He; Zhixiang Wang; Haifeng Gan; Qitao Tian; Kai Guo

doi:10.1016/j.bmcl.2016.02.063

Identification of inhibitors for vascular endothelial growth factor receptor by using dynamic combinatorial chemistry

Bioorg Med Chem Lett. 2016 Apr 1;26(7):1671-4. doi: 10.1016/j.bmcl.2016.02.063. Epub 2016 Feb 22.

Authors

Zhao Yang¹, Zheng Fang², Wei He³, Zhixiang Wang¹, Haifeng Gan³, Qitao Tian³, Kai Guo³

Affiliations

¹ School of Pharmaceutical Engineering, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing 211816, China.
² School of Pharmaceutical Science, Nanjing Technology University, No. 30 Puzhu South Road, Nanjing 211816, China.
³ College of Biotechnology and Pharmaceutical Engineering, Nanjing Technology University, No. 30 Puzhu South Road, Nanjing 211816, China.

PMID: 26920800
DOI: 10.1016/j.bmcl.2016.02.063

Abstract

The novel analysis method consisting of size-exclusion chromatography (SEC) and HRMS analysis was firstly applied in the discovery of potential inhibitors towards cancer drug targets. With vascular endothelial growth factor receptor (VEGFR-2) as a target, dynamic combinatorial libraries (DCLs) were prepared by reacting aldehydes with amines. Four sensitive binders targeted VEGFR-2 were directly isolated from the library. Antitumor activity test in vitro and inhibition experiments toward angiogenesis were also carried out.

Keywords: Drug discovery; Dynamic combinatorial chemistry; Enzyme inhibitors; Imine formation; Ligand separation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / chemistry*
Angiogenesis Inhibitors / pharmacology*
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Combinatorial Chemistry Techniques / methods
Drug Discovery
Humans
Neoplasms / blood supply
Neoplasms / drug therapy
Neovascularization, Pathologic / drug therapy
Small Molecule Libraries / chemistry*
Small Molecule Libraries / pharmacology*
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

Angiogenesis Inhibitors
Antineoplastic Agents
Small Molecule Libraries
Vascular Endothelial Growth Factor Receptor-2