Atg4B-IN-2 is a potent competitive Atg4B inhibitor with K i value of 3.1 μM, also possesses declining PLA 2 inhibitory potency, IC50 s of 11 μM and 3.5 μM for Atg4B and PLA 2, respectively. Atg4B-IN-2 enhances the anticancer activity of anti-castration-resistant prostate cancer agents via autophagy inhibition [1].
In Vitro, 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].
References:
[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.
In Vitro, 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].
References:
[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.