In Silico Discovery and Characterization of a Novel Nuclear Transcription Factor-Y (NF-Y) Inhibitor with...

Area of Science:

• Molecular Biology
• Pharmacology
• Biochemistry

Background:

• Nuclear Transcription Factor-Y (NF-Y) regulates genes controlling cell proliferation, metabolism, and differentiation.
• Dysregulation of NF-Y is implicated in various diseases, including cancer and fibrosis.
• Targeting NF-Y presents a potential therapeutic strategy for NF-Y-driven pathologies.

Purpose of the Study:

• To identify small molecules that inhibit NF-Y activity.
• To characterize the mechanism of action and therapeutic potential of identified inhibitors.

Main Methods:

• In silico molecular docking screened eight million compounds against the NF-YB/NF-YC dimer.
• NFYi5 activity was assessed by measuring mRNA levels of NF-Y target genes.
• Mechanistic studies evaluated NF-Y DNA binding and NF-YA protein stability.

Main Results:

• NFYi5 was identified as a potent inhibitor of NF-Y activity.
• NFYi5 reduced NF-Y target gene expression and inhibited cancer cell proliferation.
• NFYi5 impaired NF-Y DNA binding and decreased NF-YA protein half-life from 16.5 to 8.5 hours.

Conclusions:

• NF-Y is a pharmacologically tractable target.
• NFYi5 demonstrates antimitogenic properties and is a promising lead compound for therapeutic development.
• This study validates NF-Y as a target for treating diseases driven by its aberrant activity.