Discovery and Characterization of Uracil Derivatives Targeting the Set-and-Ring Domain of UHRF1.

ABSTRACT: The Set and Ring domain of the UHRF1 oncogene is responsible for its interaction with hemimethylated DNA and faithful propagation of epigenetic signaling over cellular replication. Inhibiting this recognition can have serious implications for UHRF1 functionality and may possibly enable therapeutic interventions. Based on a previous finding indicating a promising in vitro DNA demethylating potential of a pyrimidine derivative, a subscaffold search was performed in the NCI/DTP compound repository to discover similar molecules and evaluate their affinity for the SRA domain of UHRF1. Toward this direction, several compounds were evaluated using a thermal melt screen, and the most promising hits were subsequently studied by calorimetry in terms of their capacity to bind the 5-methylcytos

SUBMITTER: Akrani I 

PROVIDER: S-EPMC12421671 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature