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KU-55933
KU-55933

Basic Information
English Name 2-morpholino-6-(thianthren-1-yl)-4H-pyran-4-one  
Synonym ATM Kinase Inhibitor  
CAS 587871-26-9  
Molecular Formula C21H17NO3S2  
Molecular Weight 395.49  

Physical And Chemical Properties bp
nD20  
density  
fp  
Apperance  

Transportation Information
UNNumber  
Class  
PG  
Dangerous Description  
Safe Description  

Usage
KU-55933 is a potent ATM inhibitor with an IC50 and Ki of 13 and 2.2 nM, respectively; highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.  

Other Infomation

KU-55933 is a potent ATM inhibitor with an IC50 and Ki of 13 and 2.2 nM, respectively; highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.
IC50 Value: 13 nM
Target: ATM
in vitro: KU-55933 inhibits DNA-PK and PI3K with IC50 of 2.5 μM and 16.6 μM, respectively. Besides, KU-55933 also prevents the activity of mTOR with IC50 of 9.3 μM. KU-55933 is active at the cellular level in ablating a well-characterized ATM-dependent phosphorylation event. KU-55933 has a dose-dependent effect in inhibiting this ATM-dependent phosphorylation event with IC50 of 300 nM. KU-58050 does not prevent the ATM-dependent phosphorylation of p53 serine 15 until a dose of 30 μM. Addition of KU-55933 has no appreciable effects on UV-induced phosphorylation of H2AX on serine 139, NBS1 on serine 343, CHK1 on serine 345, and SMC1 on serine 966. In stark contrast to the UV responses, KU-55933 ablates the ionizing radiation-induced phosphorylation of these ATM substrates. KU-55933 sensitizes HeLa cells to a range of ionizing radiation doses. KU-55933 inhibits the phosphorylation of Akt induced by growth factors in cancer cells. KU-55933 suppresses the proliferation of cancer cells. Furthermore, suppression of ATM by KU-55933 improves survival, probably via prevention of downstream activation of TAp63α.
in vivo: Suppression of ATM-dependent STAT3 activation by KU-55933 enhances TRAIL-mediated apoptosis through up-regulation of surface DR5 expression, whereas suppression of both STAT3 and NF-κB appeares to be involved in down-regulation of cFLIP accompanied by an additional increase in apoptotic levels. The ATM inhibitor KU-55933 affectes TRAIL-mediated apoptosis more strongly than the JAK2 inhibitor, AG490, or overexpression of STAT3β.


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[2]. Khalil HS, Tummala H, Hupp TR, Zhelev N.Pharmacological inhibition of ATM by KU55933 stimulates ATM transcription.Exp Biol Med (Maywood). 2012 Jun;237(6):622-34. Epub 2012 Jun 22.


[3]. Ching JK, Luebbert SH, Collinsiv RL, Zhang Z, Marupudi N, Banerjee S, Hurd R, Ralston L, Fisher JS.Exp Physiol. 2012 Aug 31.


[4]. Choi S, Srivas R, Fu K, Hood BL, Dost B, Gibson GA, Watkins SC, Van Houten B, Bandeira N, Conrads T, Ideker T, Bakkenist CJ.Quantitative proteomics reveals ATM kinase-dependent exchange in DNA damage response complexes.J Proteome Res. 2012 Aug 21.


[5]. Kim YD, Li T, Ahn SW, Kim DK, Lee JM, Hwang SL, Kim YH, Lee CH, Lee IK, Chiang JY, Choi HS.Orphan nuclear receptor SHP negatively regulates growth hormone-mediated induction of hepatic gluconeogenesis through inhibition of STAT5 transactivation.J Biol Chem. 2012 Sep 12.


 



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