S130 is a high affinity, selectiveATG4B (a major cysteine protease) inhibitor (IC50 of 3.24 μM).It suppresses autophagy flux.

ATG4B:3.24 µM

S130 suppresses autophagy and activates apoptosis by inhibiting ATG4B, leads to enhanced cytotoxicity. S130 (0-25 μM; 48 hours) induces cell death through inhibiting the activity of ATG4B at a dose higher than 6.3 μM. And such cytotoxicity might not cause cell death through necroptosis. Nutrient deprivation enhances S130-induced cytotoxicity. S130 (0-10μM; 24 hours) suppresses approximately 79% of the cleavage of full-length LC3-GST at the 10 μM, while no substrates were processed in ATG4B KO cells. S130 displays obvious inhibitory effects on ATG4B.

Tumor growth suppressed by S130 (20 mg/kg; i.p.; daily; 3 weeks), S130 shows an efficient in vivo antitumor effect with a sound safety on vital organs.