An autophagy inhibitor
Description:
IC50: 0.6 and 0.7 μM for USP10 and USP13 activity, respectively
Autophagy is an important intracellular catabolic mechanism which mediates the degradation of cytoplasmic proteins and organelles. USP10 mediates the deubiquitination of p53, regulating deubiquitination the activities of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. Spautin-1 is a novel autophagy inhibitor.
In vitro: Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes via inhibiting two ubiquitinspecific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Spautin-1 had no effect on the growth and survival of Bcap-37 cells under normal culture conditions but dramatically enhanced cell death in glucose-free media. Under glucose-free conditions, western blotting for LC3 further confirmed that autophagy was induced, which was inhibited by spautin-1. Similar results were obtained with MCF-7 and BT549 cells. Therefore, spautin-1 can sensitize tumor cells to apoptosis under nutritional deprived conditions [1].
In vivo: So far, there is no report to investigate the in vivo animal efficacy of spautin-1.
Clinical trial: Up to now, spautin-1 is still in the preclinical development stage.
Reference:
[1] Liu J, Xia H, Kim M, Xu L, Li Y, Zhang L, Cai Y, Norberg HV, Zhang T, Furuya T, Jin M, Zhu Z, Wang H, Yu J, Li Y, Hao Y, Choi A, Ke H, Ma D, Yuan J.? Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell. 2011 Sep 30;147(1):223-34.
| Cell experiment[1]: | |
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Cell lines |
Mouse MEF cells |
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Preparation method |
The solubility of this compound in DMSO is > 13.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
4 h, 10 μM |
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Applications |
Spautin-1 is a potent and specific small molecule inhibitor of autophagy. Spautin-1 inhibits two ubiquitin-specific peptidases, USP10 and USP13 ( IC50 values of 0.6 and 0.7 μM respectively), and promotes the ubiquitination and degradation of Vps34 PI3 kinase complexes, leading to an inhibition of autophagy. |
| Animal experiment [2]: | |
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Animal models |
Female KunMing (KM) mice |
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Dosage form |
Intraperitoneal injection, 2 mg/kg |
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Application |
Pretreating mice with spautin-1 significantly reduced the elevation of serum lipase and amylase levels, which are indicators of trypsin activity. Spautin-1 also inhibited the increasing levels of serum TNFα induced by cerulein. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [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]. Xiao J, Feng X, Huang X Y, et al. Spautin-1 ameliorates acute Pancreatitis via inhibiting impaired autophagy and alleviating Calcium Overload[J]. Molecular Medicine, 2016, 22: 643. | |
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