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Overview
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Background
Amuvatinib (also known as MP-470 or HPK 56), a synthetic carbothioamide, is a novel and potent tyrosine kinase inhibitor, which exerts in vitro and in vivo activities against multiple targets including mutant KIT, platelet-derived growth factor receptor alpha (PDGFRα) and DNA repair. Μechanisticly, amuvatinib inhibits tyrosine kinase receptor KIT through occupying its ATP binding domain (IC50 < 0.1 μM) and disrupts DNA repair through suppression of homologous recombination protein Rad51 as well as synergistic effects in combination with double stranded DNA damaging agents. Recent studies have shown that amuvatinib exhibits antitumor activity against human cancer cell lines, especially GIST-48 human cell line, in which it strongly inhibits proliferation (IC50 = 0.20 μM).
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