Kingkan SanphanyaSuvara K. WattanapitayakulSuwadee PhowichitValery V. FokinOpa VajraguptaMahidol UniversitySrinakharinwirot UniversityScripps Research Institute2018-10-192018-10-192013-05-15Bioorganic and Medicinal Chemistry Letters. Vol.23, No.10 (2013), 2962-2967146434050960894X2-s2.0-84876669366https://repository.li.mahidol.ac.th/handle/20.500.14594/31310We 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 IC50against 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. © 2013 Elsevier Ltd. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1016/j.bmcl.2013.03.042