TY - JOUR T1 - Suramin potently inhibits binding of the mammalian high mobility group protein AT-hook 2 to DNA JF - bioRxiv DO - 10.1101/838656 SP - 838656 AU - Linjia Su AU - Nadezda Bryan AU - Sabrina Battista AU - Juliano Freitas AU - Alyssa Garabedian AU - Federica D’Alessio AU - Miriam Romano AU - Fabiana Falanga AU - Alfredo Fusco AU - Lidia Kos AU - Jeremy Chambers AU - Francisco Fernandez-Lima AU - Prem P. Chapagain AU - Stefan Vasile AU - Layton Smith AU - Fenfei Leng Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/12/838656.abstract N2 - The mammalian high mobility group protein AT-hook 2 (HMGA2) is a multi-functional DNA-binding protein which plays important roles in tumorigenesis and adipogenesis. Previous results showed that HMGA2 is a potential therapeutic target of anticancer and anti-obesity drugs by inhibiting its DNA-binding activities. Here we report the development of a miniaturized, automated AlphaScreen high throughput screening (HTS) assay to identify inhibitors targeting HMGA2-DNA interactions. After screening the LOPAC1280 compound library, we discovered that suramin, a negatively charged antiparasitic drug potently inhibits the HMGA2-DNA interaction. Our results also show that the inhibition is through suramin binding to the AT-hooks of HMGA2, therefore blocking its DNA binding capacity. Furthermore, we demonstrate that suramin can induce brain tumor stem cells differentiation into cells with neurite-like structures, a process triggered by disrupting HMGA2-DNA interactions. Since suramin has strong antitumor and anti-metastasis activities, our discovery suggests that HMGA2 and HMGA2-like proteins may be the cellular target of this century-old drug. ER -