Prion Protein Degrader

(R)-SM875 is a cellular prion protein (PrP) degrader with an IC₅₀ of 3 μM in HEK293 cells. (R)-SM875 interacts with PrP folding intermediates, binds to a binding pocket unique to FI-PrP, inhibits PrP^C maturation, blocks prion replication, and induces cytotoxicity, autophagy, PrP^C aggregation, as well as lysosome-dependent autophagy-mediated post-translational degradation of PrP^C, without altering the mRNA level of PrP^C. (R)-SM875 can be used in research related to prion diseases.

Keratinase (KerA) is an orally active proteolytic enzyme that specifically degrades keratin, and it is mainly secreted by microorganisms such as bacteria, fungi and actinomycetes. Keratinase degrades keratin via reducing disulfide bond cross-links and cleaving peptide bonds, and it can also degrade infectious prion proteins. Keratinase can improve the nutritional bioavailability of keratin-based feed, and it can also be applied in various fields including depilation, proteolytic cleaning, organic fertilizer precursor preparation, cosmetics, bioenergy production, wastewater decolorization, biomolecule extraction, bioremediation, textile biopretreatment and feed processing.

SM875 is a cellular prion protein (PrP) degrader (IC₅₀: 7.87 μM). SM875 targets PrP folding intermediates and promotes its degradation through the autophagy-lysosomal pathway. SM875 only acts on nascent, immature PrP molecules and has no effect on mature PrP before synthesis. SM875 can inhibit prion replication and has potential in the study of neurodegenerative diseases (i.e., prion diseases).