SM875 is a degrader specifically targeting the cellular prion protein (PrP) with an IC50 of 7.87 μM. By binding to the folding intermediates of PrP, SM875 facilitates their degradation via the autophagy-lysosome pathway. It acts exclusively on nascent, immature PrP molecules and does not affect mature PrP synthesized beforehand. SM875 has the potential to inhibit prion replication, making it a promising compound for research in neurodegenerative diseases, particularly prion diseases.