LV-320 is a potent and uncompetitive ATG4B inhibitor with an IC50 of 24.5 µM and a Kd of 16 µM. LV-320 inhibits ATG4B enzymatic activity, blocks autophagic flux in cells, and is stable, non-toxic and active in vivo.
IC50&Target
IC50: 24.5 µM (ATG4B); Kd: 16 μM (ATG4B)
体外研究
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.
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.
Western Blot Analysis
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
Cell Line:
MDA-MB-231 cells
Concentration:
120 µM
Incubation Time:
48 hours
Result:
Blocked autophagic flux.
体内研究
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.
Animal Model:
GFP-LC3 mice (females, 9-14 weeks)
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.
分子式
C29NO2S2ClH26
分子量
520.11
CAS号
2449093-46-1
运输条件
Room temperature in continental US; may vary elsewhere.