Application

YM-1 has been used as a Hsp70 (heat shock protein) inhibitor in cell viability assay.

Biochem/physiol Actions

YM-1 modulates Hsp70 activity by binding to the nucleotide-binding domain of ADP- but not ATP-bound Hsp70, stabilizing Hsp70 in its ADP-bound conformation. The ADP-bound state has tight affinity for its substrates, promoting their ubiquitination and degradation, and a greatly reduced off rate compared to the ATP-bound state. YM-1 appears to behave in a similar manner to Hip, a Hsp70 co-chaperone that stabilizes Hsp70 in its ADP-bound conformation which favors degradation of misfolded substrates such as those involved in various neurodegenerative diseases. YM-1 also has anticancer activity, which could be due to enhanced ubiquitination and clearance of Akt, a major survival kinase. In studies with multiple cancer lines, YM-1 was found to selectively target cancer cells over normal cells and to overcome tamoxifen resistance in a tamoxifen-resistant MCF7 cell model. YM-1 had greater efficacy and cytosolic localization than the closely related MKT-077 (M5449).

Packaging

5, 25 mg in glass bottle