NSC 185058 is a synthetic inhibitor of the ATG4B, with an IC50 value of 51μM [1]. NSC 185058 inhibits autophagy, which in turn suppresses the activity of mTORC1 as well as the phosphorylation status of the P70S6K and 4EBP1, thereby preventing the increase in cellular protein anabolism[2]. NSC 185058 has been widely used to prevent the replication of Enterovirus 71 (EV71) and to inhibit the infection of virus-infected cells[3].
In vitro, NSC 185058 (100µM) treatment for 72 hours significantly reduced the protein content of ATG4B in A549 cells and inhibited cell proliferation[4]. Treatment with 10µM NSC 185058 for 6 days significantly inhibited the formation of osteoclasts induced by RANKL in mouse bone marrow cells, and induced cell death[5]. Treatment with 5µM NSC 185058 for 2 hours in combination with 3Gy ionizing radiation reduced the viability of mutant IDH1 glioma cells and increased cell radiosensitivity[6].
In vivo, NSC 185058 treatment via subcutaneous injection at a dose of 100mg/kg, every other day for 5 days, significantly inhibited the growth of Saos-2 osteosarcoma in mice within 30 days, without altering the body size of the mice[7].
References:
[1] Qiu Z, Kuhn B, Aebi J, et al. Discovery of fluoromethylketone-based peptidomimetics as covalent ATG4B (autophagin-1) inhibitors[J]. ACS medicinal chemistry letters, 2016, 7(8): 802-806.
[2] Ryan P J, Uranga S, Stanelle S T, et al. The autophagy inhibitor NSC185058 suppresses mTORC1-mediated protein anabolism in cultured skeletal muscle[J]. Scientific reports, 2024, 14(1): 8094.
[3] Sun Y, Zheng Q, Wang Y, et al. Activity-based protein profiling identifies ATG4B as a key host factor for enterovirus 71 proliferation[J]. Journal of Virology, 2019, 93(24): 10.1128/jvi. 01092-19.
[4] Ryan P J, Guerra B C, Uranga S, et al. ATG4B is required for mTORC1‐mediated anabolic activity and is associated with clinical outcomes in non‐small cell lung cancer[J]. FEBS Open Bio, 2026, 16(3): 570-583.
[5] Hiura F, Kawabata Y, Aoki T, et al. Inhibition of the ATG4-LC3 pathway suppressed osteoclast maturation[J]. Biochemical and biophysical research communications, 2022, 632: 40-47.
[6] Núñez F J, Banerjee K, Mujeeb A A, et al. Autophagy Upregulation in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma Uncovers a Novel Therapeutic Target[J]. Research square, 2025: rs. 3. rs-7483444.
[7] Akin D, Wang S K, Habibzadegah-Tari P, et al. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors[J]. Autophagy, 2014, 10(11): 2021-2035.
NSC 185058是一种ATG4B的合成抑制剂，IC50值为51μM[1]。NSC 185058抑制自噬，进而抑制mTORC1 活性以及P70S6K和4EBP1的磷酸化状态，从而阻止细胞蛋白质合成代谢的增加[2]。NSC 185058已被广泛用于阻止肠道病毒71型(EV71)的复制，并抑制病毒对感染细胞的入侵[3]。
在体外，100μM的NSC 185058处理A549细胞72小时，显著降低了细胞中ATG4B的蛋白含量并抑制了细胞增殖[4]。使用10μM的NSC 185058处理小鼠骨髓细胞6天，显著抑制了RANKL诱导的破骨细胞形成，并诱导了细胞死亡[5]。将5μM的NSC 185058与3Gy电离辐射联合处理突变IDH1胶质瘤细胞2小时，降低了细胞活力并增加了细胞放射敏感性[6]。
在体内，每隔一天皮下注射100mg/kg剂量的NSC 185058，持续5天，在30天内显著抑制了小鼠体内Saos-2骨肉瘤的生长，且未改变小鼠的体型[7]。