phenylethynesulfonamide

Phenylethynesulfonamide (PES), also known as pifithrin-mu (PFT-mu), is a small molecule inhibitor of the heat shock protein 70 (HSP70) family, including the constitutively expressed HSC70. It interacts specifically with the C-terminal substrate-binding domain (SBD) of HSP70, disrupting its chaperone activity and interaction with co-chaperones. This interference leads to the aggregation of misfolded proteins, inhibition of autophagy, and destabilization of the HSP90-mediated protein folding machinery, which in turn reduces the levels of oncogenic client proteins such as HER2, AKT, and CDK4. PES has also been shown to inhibit the Anaphase Promoting Complex/Cyclosome (APC/C), inducing G2/M cell cycle arrest. It exhibits selective cytotoxicity toward cancer cells, particularly in models of melanoma and B-cell lymphoma, while sparing normal cells.

Other names

2-phenylethynesulfonamide