Novel structure motif for the selective inhibition of TET1 protein based on perimidines

• Autoři: KEJIK Zdenek; KAPLANEK Robert; ABRAMENKO Nikita; VELLIEUX Frederic; VESELA Katerina; BABULA Petr; MASAŘÍK Michal; ULRICH Jan; KUCNIROVA Katerina; HAJDUCH Jan; MARTASEK Pavel; JAKUBEK Milan
• Rok publikování: 2026
• Druh: Recenzovaný odborný článek
• Časopis / Zdroj: Journal of Molecular Structure
• Doi: https://doi.org/10.1016/j.molstruc.2025.143720
• Klíčová slova: TET proteins; Inhibitors; Iron chelators; Perimidine; Molecular docking
• Popis: The targeting of epigenetic factors, particularly TET proteins (ten-eleven translocation methylcytosine dioxygenases), has emerged as a significant focus in medicinal and biological research. Recent findings indicate that iron chelators possess substantial potential for inhibiting TET activity. In this study, we synthesized two 2-(hetero)aryl-1H-perimidines (perimidine 1 and 2) with iron(II) binding properties. The results show that these derivatives, particularly 2, exhibit notable inhibitory activity and selectivity for the TET1 protein, with an IC50 value of 1.02 mu M, in contrast to TET2, which has an IC50 value of 13.23 mu M.