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8-(4-二苯并噻吩基)-2-(4-吗啉基)-4H-1-苯并吡喃-4-酮
8-(4-二苯并噻吩基)-2-(4-吗啉基)-4H-1-苯并吡喃-4-酮

Basic Information
English Name 8-dibenzothiophen-4-yl-2-morpholin-4-ylchromen-4-one  
Synonym KU-57788  
CAS 503468-95-9  
Molecular Formula C25H19NO3S  
Molecular Weight 413.48800  

Physical And Chemical Properties bp
nD20  
density  
fp  
Apperance yellow  

Transportation Information
UNNumber  
Class  
PG  
Dangerous Description  
Safe Description  

Usage
KU-57788(NU7441)是DNA-PK选择性抑制剂,IC50为14  

Other Infomation

KU-57788(NU7441) is a potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor with IC50 value of  are 14 nM; 1700, 5000, >100000 and >100000 nM for  mTOR, PI 3K, ATM and ATR respectively; also is a modest inhibitor of BRD4 and BRDT with IC50s of 1 and 3.5 uM respectively.
IC50 value: 14 nM (DNA-PK)[1]; 1/3.5 uM(BRD4/BRDT) [4]
Target: DNA-PK; BRD4/BRDT
in vitro:  NU7441 increased the cytotoxicity of ionizing radiation and etoposide in SW620, LoVo, and V3-YAC cells but not in V3 cells, confirming that potentiation was due to DNA-PK inhibition. NU7441 substantially retarded the repair of ionizing radiation-induced and etoposide-induced DSB. NU7441 appreciably increased G(2)-M accumulation induced by ionizing radiation, etoposide, and doxorubicin in both SW620 and LoVo cells [2]. NU7441 strongly inhibited DNA-PK in cell lines (IC(50) = 0.3 μM) but only weakly inhibited PI3 K (IC(50) = 7 μM). NU7441 caused doxorubicin- and IR-induced DNA DSBs (measured by γ-H2AX foci) to persist and also slightly decreased homologous recombination activity, as assessed by Rad51 foci [3]. NU7441 is a modest inhibitor of BRD4 and BRDT (IC50 = 1 and 3.5 SM, respectively), which establishes a single hydrogen bond in the KAc site through the chromenone oxygen with Asn140 [4].
in vivo: In mice bearing SW620 xenografts, NU7441 concentrations in the tumor necessary for chemopotentiation in vitro were maintained for at least 4 hours at nontoxic doses. NU7441 increased etoposide-induced tumor growth delay 2-fold without exacerbating etoposide toxicity to unacceptable levels [2].


[1]. Leahy JJ, et al. Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6083-7.


[2]. Zhao Y, et al. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 2006 May 15;66(10):5354-62.


[3]. Tavecchio M, et al. Further characterisation of the cellular activity of the DNA-PK inhibitor, NU7441, reveals potential cross-talk with homologous recombination. Cancer Chemother Pharmacol. 2012 Jan;69(1):155-64.


[4]. Ember SW, et al. The acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors. ACS Chem Biol. 2014 Feb 25.



 


 



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