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

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

Результат исследований: Материалы для журналаСтатьярецензирование

29 Цитирования (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.

Язык оригиналаАнглийский
Страницы (с-по)2962-2967
Число страниц6
ЖурналBioorganic and Medicinal Chemistry Letters
Номер выпуска10
СостояниеОпубликовано - 15 мая 2013
Опубликовано для внешнего пользованияДа

ASJC Scopus subject areas

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

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