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].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Metabolic Enzyme/Protease >> Cathepsin

IC50: 3.24 µM (ATG4B)[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]. Cell Cytotoxicity Assay[1] Cell Line: HeLa cells, HCT116 cells, HL60 cells Concentration: 0 μM, 3.1 μM, 6.3 μM, 12.5 μM, 25 μM Incubation Time: 48 hours Result: Had significant cytotoxic effects on HeLa cells (IC50 =16.1 µM), HCT116 cells(IC50 =9.0 µM) and HL60 cells (IC50 =4.7 µM) at a dose higher than 6.3 µM. And such cytotoxicity might not cause cell death through necroptosis. Cell Autophagy Assay[1] Cell Line: HeLa cells and MEF cells Concentration: 10 μM Incubation Time: 6 hours Result: Suppressed autophagy at the early LC3 priming step or late autolysosome degradation stage. Western Blot Analysis[1] Cell Line: HeLa cells Concentration: 0 μM, 5 μM, 10 μM Incubation Time: 24 hours Result: Suppressed approximately 79% of the cleavage of full-length LC3-GST at 10 µM, while no substrates were processed in ATG4B KO cells.

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]. Animal Model: BALB/c nude female mice (4 weeks), with HCT116 cells xenograft[1] Dosage: 20 mg/kg Administration: Intraperitoneal injection; daily; 3 weeks Result: Was able to suppress tumor growth and with a sound safety on vital organs.

[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.