1262888-28-7 Usage
Description
Spautin-1 (1262888-28-7) is a specific and potent autophagy inhibitor. Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin-specific proteases USP10 and USP13 which target the Beclin-1 subunit of Vps34 complexes.1?Deranges dengue virion maturation.2?Spautin-1 inhibits autophagy in a Beclin-1 independent manner in primary epithelial ovarian cancer cells.3?Selectively induces cell death of mutant p53-expressing cancer cell lines under confluency.4?Cell permeable.
Uses
Different sources of media describe the Uses of 1262888-28-7 differently. You can refer to the following data:
1. Spautin-1 is a potent pharmacological autophagy inhibitor that promotes UVB-induced tumorigenesis. It is also a small-molecule drug that modulate autophagic pathways in different types of cancer.
2. Spautin-1 has been used as an autophagy inhibitor:to study its effects on vascular, glial, and neuronal alterations in the oxygen-induced retinopathy mouse modelto evaluate its pre-treatment effect on the response of canine osteosarcoma cells to doxorubicinto study its effects on the production of interleukin (IL)-6 by oxidatively stressed dendritic cells (OS-DCs) in Luminex assay
Biochem/physiol Actions
Spautin-1 inhibits the activity of two ubiquitin-specific peptidases, USP10 and USP13, causing an increase in proteasomal degradation of class III PI3 kinase complexes, which have been shown to regulate autophagy.
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].
IC 50
0.6 and 0.7 μm for usp10 and usp13 activity, respectively
References
1) Liu et al. (2011), Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13; Cell, 147 223
2) Mateo et al. (2013), Inhibition of cellular autophagy deranges dengue virion maturation; J. Virol., 87 1312
3) Correa et al. (2014), Combination of AKT inhibition with autophagy blockade effectively reduces ascites-derived ovarian cancer cell viability; Carcinogenesis,?35 1951
4) Vakifahmetoglu-Norburg et al. (1987), Chaperone-mediated autophagy degrades mutant p53; Genes Dev., 27 1718
Check Digit Verification of cas no
The CAS Registry Mumber 1262888-28-7 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,6,2,8,8 and 8 respectively; the second part has 2 digits, 2 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1262888-28:
(9*1)+(8*2)+(7*6)+(6*2)+(5*8)+(4*8)+(3*8)+(2*2)+(1*8)=187
187 % 10 = 7
So 1262888-28-7 is a valid CAS Registry Number.
1262888-28-7Relevant articles and documents
Synthesis, modelling, and anticonvulsant studies of new quinazolines showing three highly active compounds with low toxicity and high affinity to the GABA-A receptor
Zayed, Mohamed F.,Ihmaid, Saleh K.,Ahmed, Hany E.A.,El-Adl, Khaled,Asiri, Ahmed M.,Omar, Abdelsattar M.
, (2017/03/09)
Some novel fluorinated quinazolines (5a-j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, 1H nuclear magnetic resonance (NMR), 13C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds 5b, 5c, and 5d showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization.
POTENT SMALL MOLECULE INHIBITORS OF AUTOPHAGY, AND METHODS OF USE THEREOF
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Page/Page column 54-55, (2011/02/24)
Certain aspects of the invention relates to small molecule autophagy inhibitors, and their use for treatment and prevention of cancers and acute pancreatitis. As disclosed herein, a small molecule inhibitor of autophagy was been identified from an image-based screen in a known bioactive library. It was found that this autophagy inhibitor functions by promoting the degradation of type III PI3 kinase complex which is required for initiating autophagy. Medicinal chemistry studies led to small molecular autophagy inhibitors with improved potency and selectivity.
