Researchers identify NFYi5, a small-molecule inhibitor of transcription factor NF-Y

Summary of Ebrahimighaei et al. (J. Med. Chem., 2026): BondLab researchers report NFYi5, a small-molecule inhibitor of transcription factor NF-Y, identified after in silico screening of 160 million compounds on Bristol’s BlueCrystal supercomputer.

Source: Journal of Medicinal Chemistry (doi:10.1021/acs.jmedchem.5c03508)

Schematic of in silico docking identifying NFYi5 and its effects on NF-Y dependent gene expression and cell proliferation — Figure from Ebrahimighaei et al., *J. Med. Chem.* (2026; © American Chemical Society). Shown for context in this summary only.

The authors targeted nuclear transcription factor Y (NF-Y), a heterotrimeric complex involved in control of genes linked to cell growth and metabolism. Transcription factors are often difficult to inhibit with small molecules; the paper describes an in silico screen to identify candidate ligands.

Using the University of Bristol BlueCrystal supercomputer and the Bristol University Docking Engine (BUDE), the team screened 160 million compound structures and advanced a hit termed NFYi5. In reported assays, NFYi5 reduced NF-Y-dependent transcriptional activity and decreased proliferation of cardiac fibroblasts, a model relevant to fibrosis. The authors also discuss literature linking NF-Y to cancer biology.

Portrait of Dr Reza Ebrahimghaei — Dr Reza Ebrahimghaei (The Bond Lab; photograph courtesy of the author).

Biochemical data in the article are consistent with NFYi5 interfering with DNA binding by NF-Y and with accelerated turnover of the NF-YA subunit. The authors conclude that NF-Y may be pharmacologically tractable with further medicinal-chemistry optimisation.

Molecular views of NFYi5 bound in the NF-Y protein pocket — Figure from Ebrahimighaei et al., *J. Med. Chem.* (© American Chemical Society).

For structures, assay conditions, and limitations, see Ebrahimighaei et al., Journal of Medicinal Chemistry (doi:10.1021/acs.jmedchem.5c03508).