LV-320

LV-320 is a potent and uncompetitive ATG4B inhibitor with an IC₅₀ 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^[1]. IC50 & Target: IC50: 24.5?μM (ATG4B); Kd: 16 μM (ATG4B)^[1] In Vitro: LV-320 (0-120?μM; SKBR3, MCF7, JIMT1, and MDA-MB-231 cells) treatment results in 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]. In Vivo: LV-320 (100-200?mg/kg; oral gavage; three times over two days; GFP-LC3 mice) treatment results in 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].