Atg4B-IN-2

Atg4B-IN-2 is a potent competitive Atg4B inhibitor with Ki value of 3.1 μM, also possesses declining PLA2 inhibitory potency, IC50s of 11 μM and 3.5 μM for Atg4B and PLA2, respectively. Atg4B-IN-2 enhances the anticancer activity of anti-castration-resistant prostate cancer drugs via autophagy inhibition[1].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Phospholipase

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Metabolic Enzyme/Protease >> Cathepsin

IC50: 11 μM (Atg4B), 3.5 μM (PLA2)[1] Ki: 3.1 μM (Atg4B)[1]

Atg4B-IN-2 (compound 21f) (1-10 μM; 2 hours) restores the p62 expression in cells treated with AF (amino acid-free) in a dose-dependent manner[1]. Atg4B-IN-2 (1 and 5 μM; 2 hours) decreases moderately autophagic vesicles at 1 μM, and almost completely inhibits autophagy at 5 μM[1]. Atg4B-IN-2 (5 μM; 2 hours) inhibits Abi-induced autophagy and significantly augments apoptotic cell death and sensitivity to Abi[1]. Western Blot Analysis Cell Line: LNCaP cells (incubated in AF medium)[1] Concentration: 1, 2, 5, 10 μM Incubation Time: 2 hours (then incubated in AFM for 24 or 3 hours) Result: Restored the p62 expression in cells treated with AF in a dose-dependent manner. Cell Autophagy Assay Cell Line: LNCaP cells (incubated in AF medium)[1] Concentration: 1 and 5 μM Incubation Time: 2 hours (then incubated in AFM for 24 or 3 hours) Result: Decreased moderately autophagic vesicles at 1 μM, and almost completely inhibited autophagy at 5 μM.

[1]. Kudo Y, Endo S, Fujita M, et al. Discovery and Structure-Based Optimization of Novel Atg4B Inhibitors for the Treatment of Castration-Resistant Prostate Cancer. J Med Chem. 2022;65(6):4878-4892.