| Description | LV-320 is a potent and uncompetitive ATG4B inhibitor with an IC 50 of 24.5 μM and a K d of 16 μM. LV-320 inhibits ATG4B enzymatic activity, blocks autophagic flux in cells, and is stable, non-toxic and active in vivo. These findings suggest that LV-320 will serve as a relevant chemical tool to study the various roles of ATG4B in cancer and other contexts [1]. |
| In vitro | LV-320 (0-120 μM; SKBR3, MCF7, JIMT1, and MDA-MB-231 cells) treatment leads to a dose-dependent increase in endogenous LC3B-II and protein p62 levels in all four cell lines [1]. LV-320 (120 μM; 48 hours; MDA-MB-231 cells) treatment results in an increase in LC3B-II, indicating that LV-320 blocks autophagic flux [1]. Western Blot Analysis [1] Cell Line: SKBR3, MCF7, JIMT1, and MDA-MB-231 cells Concentration: 0 μM, 25 μM, 50 μM, 75 μM, 100 μM, or 120 μM Incubation Time: Result: Resulted in a dose-dependent increase in endogenous LC3B-II and protein p62 levels in all four cell lines. Cell Autophagy Assay [1] Cell Line: MDA-MB-231 cells Concentration: 120 μM Incubation Time: 48 hours Result: Blocked autophagic flux. |
| In vivo | LV-320 (100-200 mg/kg; oral gavage; three times over two days; GFP-LC3 mice) treatment leads to a terminal blood level of 169 μM and a liver level of 104 μM. The expression of GFP-LC3 puncta is significantly greater accumulation in LV-320 treated animals compared to controls. LC3B-II protein is also increased in LV-320-treated animals. The treatment do not cause significant toxicity in mice at either dose [1]. Animal Model: GFP-LC3 mice (females, 9-14 weeks) [1] Dosage: 100 mg/kg or 200 mg/kg Administration: Oral gavage; three times over two days (Pharmacokinetic study) Result: Terminal blood levels were 169 μM and liver levels were 104 μM. LC3B-II protein level was also increased. |
| Target activity | ATG4B:(kd)16 μM , ATG4B:24.5 µM |
| molecular weight | 520.11 |
| Molecular formula | C29H26ClNO2S2 |
| CAS | 2449093-46-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 135 mg/mL (259.56 mM), Sonication is recommended. |
| References | 1. Bosc D, et al. A new quinoline-based chemical probe inhibits the autophagy-related cysteine protease ATG4B. Sci Rep. 2018 Aug 3;8(1):11653. doi: 10.1038/s41598-018-29900-x. |