Synthesis and evaluation of a near-infrared fluorescent non-peptidic bivalent integrin αvβ3 antagonist for cancer imaging

Feng Li, Jiacheng Liu, Gouri S. Jas, Jiawei Zhang, Guoting Qin, Jiong Xing, Claudia Cotes, Hong Zhao, Xukui Wang, Laura A. Diaz, Zheng Zheng Shi, Daniel Y. Lee, King C P Li, Zheng Li

Research output: Contribution to journalArticle

23 Scopus citations


Computer modeling approaches to identify new inhibitors are essentially a very sophisticated and efficient way to design drugs. In this study, a bivalent nonpeptide intergrin αvβ3 antagonist (bivalent IA) has been synthesized on the basis of an in silico rational design approach. A near-infrared (NIR) fluorescent imaging probe has been developed from this bivalent compound. In Vitro binding assays have shown that the bivalent IA (IC50 ) 0.40 ± 0.11 nM) exhibited improved integrin αvβ3 affinity in comparison with the monovalent IA (IC50 ) 22.33 ± 4.51 nM), resulting in an over 50-fold improvement in receptor affinity. NIR imaging probe, bivalent-IA-Cy5.5 conjugate, also demonstrated significantly increased binding affinity (IC50 ) 0.13 ± 0.02 nM). Fluorescence microscopy studies showed integrin-mediated endocytosis of bivalent-IA-Cy5.5 in U87 cells which was effectively blocked by nonfluorescent bivalent IA. We also demonstrated tumor accumulation of this NIR imaging probe in U87 mouse xenografts.

Original languageEnglish (US)
Pages (from-to)270-278
Number of pages9
JournalBioconjugate chemistry
Issue number2
StatePublished - Feb 17 2010

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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