6-fluoro-N-(4-fluorobenzyl)quinazolin-4-aMine

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.1Deranges dengue virion maturation.2Spautin-1 inhibits autophagy in a Beclin-1 independent manner in primary epithelial ovarian cancer cells.3Selectively induces cell death of mutant p53-expressing cancer cell lines under confluency.4Cell permeable.

Uses

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.

Uses

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 model
• to evaluate its pre-treatment effect on the response of canine osteosarcoma cells to doxorubicin
• to 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.

Synthesis

16499-61-9

140-75-0

1262888-28-7

GENERAL METHOD: 4-Chloro-6-fluoroquinazoline (1.84 g, 10 mmol), trimethylamine (1.06 g, 10 mmol) were mixed with p-fluorobenzylamine (10 mmol) in 5 mL N,N-dimethylformamide (DMF). The reaction mixture was heated to reflux for 4 h, subsequently cooled to room temperature and decanted into crushed ice. The precipitated solid was collected by filtration and purified by recrystallization with ethanol. The melting points of the resulting 6-fluoro-N-(4-fluorobenzyl)quinazolin-4-amines were all above 300 °C.

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

storage

Store at +4°C

References

[1] JUNLI LIU. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13.[J]. Cell, 2011, 147 1: 223-234. DOI:10.1016/j.cell.2011.08.037
[2] ROBERTO MATEO. Inhibition of cellular autophagy deranges dengue virion maturation.[J]. Journal of Virology, 2013, 87 3: 1312-1321. DOI:10.1128/jvi.02177-12
[3] ROHANN J M CORREA. Combination of AKT inhibition with autophagy blockade effectively reduces ascites-derived ovarian cancer cell viability.[J]. Carcinogenesis, 2014, 35 9: 1951-1961. DOI:10.1093/carcin/bgu049
[4] HELIN VAKIFAHMETOGLU-NORBERG. Chaperone-mediated autophagy degrades mutant p53.[J]. Genes & development, 2013, 27 15: 1718-1730. DOI:10.1101/gad.220897.113