S130

S130 is a high affinity, selective inhibitor of ATG4B (a major cysteine protease) with an IC50 of 3.24 µM. S130 suppresses autophagy flux[1].

S130 suppresses autophagy and activates apoptosis by inhibiting ATG4B, leads to enhanced cytotoxicity[1].S130 (10 μM; 6 hours) suppresses autophagy at the early LC3 priming step or late autolysosome degradation stage[1].S130 accumulates autolysosomes with more lipidated LC3[1].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[1].Nutrient deprivation enhances S130-induced cytotoxicity[1].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[1].

S130 (20 mg/kg; i.p.; daily; 3 weeks) suppresses tumor growth, and shows an efficient in vivo antitumor effect with a sound safety on vital organs[1].

[1]. Fu Y, et al. Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo. Autophagy. 2018 Sep 20:1-17.