Spautin-1 inhibited the deubiquitinating activity of USP10 and USP13 with IC50 values of 0.6-0.7µM [1]. As an autophagy inhibitor, Spautin-1 has been widely used to induce cell death in a variety of cancer cell models[2].
In vitro, Spautin-1 treatment for 72 hours significantly inhibited the growth of melanoma cells, with the IC50 values of 1.830 and 2.062μM against A375 and SK-Mel-28, respectively[3]. Treatment of U87MG cells with 10μM Spautin-1 for 48h significantly inhibited cell viability, the RAF-ERK pathway, and glycolytic function in the cells[4]. Pretreatment of PC12 cells with 10μM Spautin-1 for 24 hours reduced the accumulation of reactive oxygen species (ROS) and the number of autophagic microsomes induced by oxygen-glucose deprivation/reoxygenation (OGD/R) treatment, and increased cell viability[5].
In vivo, Spautin-1 treatment via intraperitoneal injection at a dose of 20mg/kg/day for 14 days significantly inhibited tumor volume growth in a mouse model of the A20 cell xenograft, and resulted in tumor cell shrinkage, fragmentation, and disorganization, as well as reduced PCNA expression[6]. In a mouse model of acute lung injury (ALI), a single dose of Spautin-1 (0.5mg/kg) intratracheal administration for 72 hours effectively reversed lipopolysaccharide (LPS)-induced lung tissue structural damage, alveolar septum thickening, and peripheral neutrophil infiltration[7]. In a mouse model of prostate cancer, Spautin-1 treatment (20mg/kg/day; i.p.) for 30 days resulted in a significant reduction in tumor weight and volume without affecting mouse body weight[8].
References:
[1] Liu J, Xia H, Kim M, et al. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13[J]. Cell, 2011, 147(1): 223-234.
[2] Schott C R, Ludwig L, Mutsaers A J, et al. The autophagy inhibitor spautin-1, either alone or combined with doxorubicin, decreases cell survival and colony formation in canine appendicular osteosarcoma cells[J]. PloS one, 2018, 13(10): e0206427.
[3] Guo J, Zhang J L, Liang L, et al. Potent USP10/13 antagonist spautin‐1 suppresses melanoma growth via ROS‐mediated DNA damage and exhibits synergy with cisplatin[J]. Journal of Cellular and Molecular Medicine, 2020, 24(7): 4324-4340.
[4] Kona S V, Kalivendi S V. The USP10/13 inhibitor, spautin-1, attenuates the progression of glioblastoma by independently regulating RAF-ERK mediated glycolysis and SKP2[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2024, 1870(7): 167291.
[5] Liu H, Zhao Z, Wu T, et al. Inhibition of autophagy‐dependent pyroptosis attenuates cerebral ischaemia/reperfusion injury[J]. Journal of Cellular and Molecular Medicine, 2021, 25(11): 5060-5069.
[6] Wu J, Deng Y, Gao Y, et al. Spautin-1 inhibits the growth of diffuse large B-cell lymphoma by inducing mitochondrial damage-mediated PANoptosis and anti-tumor immunity[J]. Cancer Immunology, Immunotherapy, 2025, 74(9): 293.
[7] Wen H, Miao W, Liu B, et al. SPAUTIN-1 alleviates LPS-induced acute lung injury by inhibiting NF-κB pathway in neutrophils[J]. International Immunopharmacology, 2024, 130: 111741.
[8] Liao Y, Guo Z, Xia X, et al. Inhibition of EGFR signaling with Spautin-1 represents a novel therapeutics for prostate cancer[J]. Journal of Experimental & Clinical Cancer Research, 2019, 38(1): 157.
Spautin-1可抑制去泛素化酶USP10和USP13的活性，IC50值为0.6-0.7µM[1]。作为自噬抑制剂，Spautin-1已被广泛应用于多种癌细胞模型的细胞死亡诱导研究[2]。
在体外，Spautin-1处理72小时可显著抑制黑色素瘤细胞生长，对A375和SK-Mel-28细胞的IC50值分别为1.830μM和2.062μM[3]。10μM的Spautin-1处理U87MG细胞48小时能显著抑制细胞活力、RAF-ERK通路及糖酵解功能[4]。10μM的Spautin-1预处理PC12细胞24小时可减少氧糖剥夺/再灌注（OGD/R）诱导的活性氧（ROS）积累和自噬微体数量，并提高细胞活力[5]。
在体内，A20细胞异种移植小鼠模型每日腹腔注射Spautin-1（20mg/kg/day；持续14天）可显著抑制肿瘤体积增长，导致肿瘤细胞萎缩、碎裂和结构紊乱，并降低PCNA表达[6]。急性肺损伤（ALI）小鼠模型单次气管内注射Spautin-1（0.5mg/kg；72小时）能有效逆转脂多糖（LPS）诱导的肺组织结构损伤、肺泡隔增厚及中性粒细胞浸润[7]。前列腺癌小鼠模型每日腹腔注射20mg/kg剂量的Spautin-1（持续30天）可显著降低肿瘤重量和体积，且不影响小鼠体重[8]。