In summary, we have examined several thioamide peptide scaffolds and identified one peptide, RS1A, that is not only resistant to proteolysis by all five cathepsins (Cts L, Cts V, Cts K, Cts S, and Cts B), but is also a potent, specific inhibitor of Cts L. This peptide can reversibly inhibit Cts L without degradation in HepG2 liver cancer cell lysate and shows promising activity in MDA-MB-231 breast cancer cells. Here, CTSS is linked to breast cancer.