| Identification | Back Directory | [Name]
6-fluoro-N-(4-fluorobenzyl)quinazolin-4-aMine | [CAS]
1262888-28-7 | [Synonyms]
C43
CS-1649
Spautin-1
SPAUTIN-1;SPAUTIN1
Spautin 1 - MBCQ derivative C43
6-Fluoro-N-(4-fluorobenzyl)-4-quinazolinamine
4-((4-Fluorobenzyl)amino)-6-fluoroquinazoline
6-fluoro-N-(4-fluorobenzyl)quinazolin-4-aMine
6-Fluoro-N-(4-fluorobenzyl)quinazolin-4-amine 98+%
6-Fluoro-N-[(4-fluorophenyl)methyl]-4-quinazolinamine
6-Fluoro-N-[(4-fluorophenyl)methyl]quinazolin-4-amine
4-Quinazolinamine, 6-fluoro-N-[(4-fluorophenyl)methyl]- | [Molecular Formula]
C15H11F2N3 | [MDL Number]
MFCD16962292 | [MOL File]
1262888-28-7.mol | [Molecular Weight]
271.265 |
| Chemical Properties | Back Directory | [Melting point ]
211 °C | [Boiling point ]
419.6±40.0 °C(Predicted) | [density ]
1.366±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: soluble15mg/mL (clear solution) | [form ]
powder | [pka]
5.75±0.50(Predicted) | [color ]
white to beige | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months. |
| Hazard Information | Back Directory | [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]
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
| [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. | [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]
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 -20°C | [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 |
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