PIK5-12d effectivelydegraded PIKfyve with a DC50 value of 1.48 nM and a Dmax value of 97.7% in prostate cancer VCaP cells.Mechanistic studies showed that PIK5-12d induced PIKfyvedegradation through the VHL- and proteasome-dependent manner. The gene discussed is VHL; the disease is prostate carcinoma.