NSC 185058

NSC 185058 (CAS No.: 39122-38-8) is a small-molecule inhibitor of ATG4B, a cysteine protease that plays a critical role in autophagy through the processing and activation of LC3B during autophagosome formation. By directly inhibiting ATG4B enzymatic activity, NSC 185058 attenuates autophagic flux, as evidenced by reduced LC3B lipidation and suppression of starvation-induced autophagic vacuole formation in multiple cancer cell lines, including Saos-2 and MDA-MB-468 cells. Its inhibitory activity is observed in the low micromolar range in biochemical assays and is associated with decreased protein turnover under nutrient-deprived conditions, with effects comparable to established autophagy inhibitors. Mechanistically, NSC 185058 acts independently of upstream PI3K and mTOR signaling pathways, supporting a direct modulation of the autophagy machinery. In vivo, it has demonstrated the ability to reduce autophagic vacuole formation and inhibit tumor growth in xenograft models, including osteosarcoma and glioblastoma, where it also enhances sensitivity to radiotherapy. This compound is widely utilized in studies investigating autophagy regulation, cancer cell survival, and therapeutic resistance, with experimental concentrations or dosing regimens varying according to specific cellular or animal model systems and research objectives.