Reversible Cathepsin B Inhibitor Lead Series
Cathepsin B is an abundant and ubiquitously expressed cysteine peptidase involved in many pathological processes, such as inflammation, parasite infection and cancer. To date, most cathepsin B inhibitors are short peptides or small molecules that bind covalently to the enzyme, which is a generally unfavoured feature for drugs. A novel lead series of non-covalent cathepsin B inhibitors has been identified and characterized. Ease of synthesis and favourable properties like good solubility will allow further development and optimization for preclinical testing on a short timescale. Activity, selectivity, cytotoxicity and solubility data has been compiled for a series of about 50 compounds and an SAR has been established. Next steps will involve in vivo testing and further optimization of the lead series.
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