Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach

Kingkan Sanphanya, Suvara K. Wattanapitayakul, Suwadee Phowichit, Valery V. Fokin, Opa Vajragupta

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


We report a novel VEGFR-2 inhibitor, developed by the back-to-front approach. Docking experiments indicated that the 3-chloromethylphenylurea motif of the lead compound occupied the back pocket of VEGFR-2 kinase. An attempt was made to enhance the binding affinity of 1 by expanding the structure to access the front pocket using a triazole linker. A library of 1,4-(disubstituted)-1H-1, 2,3-triazoles were screened in silico, and one compound (VH02) was identified with an IC50 against VEGFR-2 of 0.56 μM. VH02 showed antiangiogenic effects, inhibiting tube formation in HUVEC cells (EA.hy926) at 0.3 μM, 13 times lower than its cytotoxic dose. These enzymatic and cellular activities suggest that VH02 has potential as a lead for further optimization.

Original languageEnglish
Pages (from-to)2962-2967
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number10
Publication statusPublished - 15 May 2013
Externally publishedYes


  • VEGFR-2 KDR VEGFR-2 inhibitor Molecular modeling Antiangiogenesis 1,4-Disubstituted 1,2,3-triazoles CuAAC reaction

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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