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PIK5-12d is a highly active and selective PIKfyve degrader constructed based on the PIKfyve inhibitor Apilimod and VHL ligand. The compound induced PIKfyve degradation with a DC50 value of 1.5 nM and a Dmax of 97.7% could be achieved after treating prostate cancer VCaP cells for 24 h. The PIK5-12d was also found to be highly active and highly selective for PIKfyve degradation. Secondly, PIK5-12d could effectively inhibit the autophagy pathway in a variety of prostate cancer cells by degrading PIKfyve and significantly induced obvious vacuolization of tumor cytoplasm. In terms of VCaP cell proliferation inhibition, the degrader PIK5-12d was more advantageous compared to the inhibitor Apilimod. In addition, PIK5-12d was effective in inducing PIKfyve degradation as well as inhibiting tumor growth in a human-derived tissue xenograft (PDX) model.PIK5-12d, as the first highly active and selective PIKfyve degrader, may serve as a valuable tool molecule to explore the feasibility of targeting PIKfyve as a therapeutic oncology strategy.
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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