KU-60019

Biological Activity

KU-60019 is a potent ATM kinase inhibitor with IC50 of 6.3 nM. KU-60019 exhibits little to no nonspecific target effects, displaying similar target selectivity to KU 55933. KU-60019 inhibited the phosphorylation of the major DNA damage effectors p53, H2AX and KAP1 as well as AKT. KU-60019 effectively radiosensitizes human glioma cells with dose-enhancement ratio of 1.7 and 4.4 at 1 μM and 10 μM, respectively, and also radiosensitizes the normal fibroblasts but not the A-T fibroblasts. KU-60019 has also been shown to Inhibit invasion and migration of human glioma cells in vitro. KU-60019 is 10-fold more effective than KU-55933 at blocking radiation-induced phosphorylation of key ATM targets in human glioma cells. KU-60019 treatment (3 μM) blocks basal and insulin-induced AKT S473 phosphorylation by 70% and ~50%, respectively, and completely reduces radiation-induced AKT phosphorylation below the level of control.

Product Citations

• 

  BMC Biol. 2021 May 20;19(1):108.

  Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans
  KU-60019 purchased from AbMole

• 

  Nat Commun. 2019 Dec 20;10(1):5799.

  Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells.
  KU-60019 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Med Sci Monit (2017). Figure 4.KU-60019
	Method	Proliferation assay
	Cell Lines	PA-SMCs
	Concentrations	0.1 μM, 0.3 μM, 0.5 μM
	Incubation Time	24 h
	Results	The results demonstrated that at a concentration of 0.5 μM, KU60019 increased cell growth more noticeably compared with other groups

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

[1] Golding SE, et al. Cell Cycle. Dynamic inhibition of ATM kinase provides a strategy for glioblastoma multiforme radiosensitization and growth control.

[2] Golding SE, et al. Mol Cancer Ther. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion.