ARN25499 is a novel Cdc42 GTPase interaction inhibitor. It inhibits the interaction between Cdc42 and its downstream effectors (i.e PAK) instead of the Cdc42-GEF interaction. ARN25499 displayed activity against four melanoma cancer cell lines (IC50s: SKM28 13.5 µM, SKMeI3 8.1 µM, WM3248 12.8 µM, A375 9.7 µM) and one colon cancer line (IC50 = 11.2 µM SW480). It also displayed good pharmacokinetics in mice. ARN25499 also showed in vivo efficacy in melanoma PDX tumors in NSG mice at 10mg/kg.
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