Kim, Byung-Hak Lee, Yoonji Yoo, Hyun Cui, Minghua Lee, Sungwoon Kim, Sun Young Cho, Jong Un Lee, Hyangsook Yang, Beom-Seok Kwon, Young-Guen Choi, Sun Kim, Tae-Yoon 2024-01-20T06:33:41Z 2024-01-20T06:33:41Z 2022-01-25 2015-07 0906-6705 https://pubs.kist.re.kr/handle/201004/125248 Vascular endothelial growth factor receptor-2 (VEGFR-2) and Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signalling are important for tumor angiogenesis and metastasis. In this study, we identified (3-(2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridin-7-ylamino)phenol (LCB03-0110) as a potent angiogenesis inhibitor. LCB03-0110 inhibited VEGFR-2 and JAK/STAT3 signalling in primary cultured human endothelial cells and cancer cells. An in vitro kinase assay and molecular modelling revealed that LCB03-0110 inhibited VEGFR-2, c-SRC and TIE-2 kinase activity via preferential binding at the ATP-binding site of their kinases. LCB03-0110 successfully occupied the hydrophobic pocket of VEGFR-2, c-SRC and TIE-2. LCB03-0110 also inhibited hypoxia-induced HIF/STAT3 and EGF- or angiopoietin-induced signalling cascades. In addition, LCB03-0110 inhibited VEGF-induced proliferation, viability, migration and capillary-like tube formation. LCB03-0110 also suppressed the sprouting of endothelial cells in the rat aorta and the formation of new blood vessels in the mouse Matrigel plug assay, but also suppressed pulmonary metastasis and tumor xenograft in mice. Our results suggest that LCB03-0110 is a potential candidate small molecule for blocking angiogenesis mediated by aberrant activation of VEGFR-2 and JAK/STAT3 signalling. English WILEY Anti-angiogenic activity of thienopyridine derivative LCB03-0110 by targeting VEGFR-2 and JAK/STAT3 Signalling Article 10.1111/exd.12698 1 EXPERIMENTAL DERMATOLOGY, v.24, no.7, pp.503 - 509 EXPERIMENTAL DERMATOLOGY 24 7 503 509 N scie scopus 000356693000007 2-s2.0-84931411333 Dermatology Dermatology Article ENDOTHELIAL GROWTH-FACTOR TYROSINE KINASE INHIBITOR TUMOR ANGIOGENESIS CRYSTAL-STRUCTURE STAT3 BIOLOGY PHOSPHORYLATION ANGIOPOIETIN EXPRESSION RECEPTORS angiogenesis JAK STAT3 LCB03-0110 VEGFR-2