NSH76: a selective inhibitor of RRN3 and RNA polymerase I transcription with potential for cancer therapy.

ABSTRACT:

Background

Aberrant upregulation of RNA polymerase I (Pol I) transcription and its dedicated machinery plays a pivotal role in tumor progression and chemoresistance. RRN3, a Pol I-specific transcription initiation factor, is frequently overexpressed in malignancies contributing to oncogenic processes. Despite the therapeutic potential of Pol I transcription inhibition, existing inhibitors lack specificity and are associated with DNA damage, mutagenicity, and toxicity, limiting their clinical utility. To fully realize the potential of Pol I-targeted cancer therapies, selective Pol I transcription inhibitors with minimal off-target effects are essential.

Methods

Molecular docking and virtual screening were conducted to identify ligands targeting RRN3. Biochemical and spectrosc

SUBMITTER: Sarkar SS 

PROVIDER: S-EPMC12538875 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature