spautin-1

Spautin-1 is a **potent and selective small molecule autophagy inhibitor** that targets the deubiquitinating enzymes USP10 and USP13, inhibiting their activity (IC50 = 0.6–0.74 μM)[1][5][6]. This results in increased ubiquitination and degradation of **Beclin1** and **VPS34**, which destabilizes the VPS34 PI3 kinase complex, a critical regulator of early autophagy[1][3][6]. Spautin-1 is used as a research tool for studying autophagy and has demonstrated **anticancer activity** by sensitizing cancer cells to apoptosis in nutrient-deprived conditions, acting synergistically with chemotherapeutic agents such as imatinib and enzalutamide[2][4][5]. Beyond autophagy inhibition, spautin-1 also **inhibits mitochondrial complex I**, suppressing the unfolded protein response and cell survival during glucose starvation, and displays **preferential cytotoxicity toward glucose-starved cancer cells**[3]. Uniquely, spautin-1 can **promote PINK1-PRKN-dependent mitophagy** under stress by stabilizing full-length PINK1 at the outer mitochondrial membrane via interactions with the TOMM complex (TOMM70 and TOMM20), which is correlated with improved neuronal function in *C. elegans* models of Alzheimer's disease[6][8]. Currently, spautin-1 is in the **preclinical research stage** with no approved clinical applications[5].

Brand names

spautin-1spautin1spautin 1

Other names

spautin-1spautin1spautin 1specific and potent autophagy inhibitor-1