KU-60019

Catalog No.S1570

Molecular Weight(MW): 547.67

KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer.

5 Customer Reviews

The ATM-dependent Ser15-p53 phosphorylation was monitored by Western blotting. Protein loading levels were monitored by probing for actin.

Brain Pathol, 2012, 22(5): 677-88 . KU-60019 purchased from Selleck.

Relative quantification of stem cell markers (Prom1, Bmi1, CD15, Msi1, Msi2, Nanog, Nestin, Oct4 and Sox2) in control BORRU epidermal growth factor fibroblast growth factor (EGF-FGF) and radiation-survived BORRU after sensitization with KU-60019 [(EGF-FGF) + KU-60019 + 5 Gy]. BORRU under differentiative conditions [fetal calf serum (FCS)] were used as tissue control (DCtref).

Brain Pathol, 2012, 22(5): 677-88 . KU-60019 purchased from Selleck.
(a,b) Drug synergy experiment in AALE cells with ATM inhibitor (KU60019) and trametinib (40 nM). Displayed is relative cell viability for KU60019 treatment alone and for co-treatment with trametinib. Error bars indicate s.d. (n=3). (b) Deviation from Bliss additivity calculated from experiment in a. Error bars indicate s.d. (n=3).

Nat Commun, 2016, 7:13701. KU-60019 purchased from Selleck.

Brain Pathol 2012 22(5), 677-88. KU-60019 purchased from Selleck.
Exp Cell Res, 2018, 366(1):24-33. KU-60019 purchased from Selleck.

Purity & Quality Control

Choose Selective ATM/ATR Inhibitors

Biological Activity

Description

Features

Improved analog of KU-55933, and is more effective at blocking ATM-mediated DDR events.

Targets

ATM ^[1]
(Cell-free assay)

6.3 nM

In vitro

Compared to KU-55933, KU-60019 is an improved more water-soluble inhibitor of the ATM kinase, while displaying similar target selectivity. KU-60019 has little activity against DNA-PKcs and ATR with IC50 values of 1.7 μM and >10 μM, respectively, as well as 229 other protein kinases such as PI3K, mTOR and mTOR/FKBP12. KU-60019 displays 3- to 10-fold more potency than KU-55933 at blocking radiation-induced phosphorylation of key ATM protein targets such as p53, γ-H2AX, and CHK2, in human glioma U87 and U1242 cells, as 1 μM of KU-60019 significantly induces >70% decrease of p53 (S15) phosphorylation to which extent ~10 μM of KU-55933 is required to achieve. 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 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. The effect of KU-60019 on AKT S473 phosphorylation can be seen in glioma cell lines and normal fibroblasts but not in A-T (h-TERT) cells, and can be significantly blocked by phosphatase inhibitor okadaic acid, suggesting a critical role of ATM kinase in regulating AKT phosphorylation via unknown phosphatase. Consistent with the inhibition of prosurvival AKT signaling, KU-60019 at 3 μM significantly inhibits migration and invasion of human glioma U87 cells by >70% and ~60%, respectively, as well as U1242 cells by >50% and ~60% respectively. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
BAECs	NW\4eo1vTnWwY4Tpc44hSXO\|YYm=	MnnCNVDDqM7:TR?=	MYixxsBpyqB?	NXzvO2F5TE2VTx?=	MnfHZYJwdGm\|aHXzJJRp\SCyaH;zdIhwenmuYYTpc44hd2ZiQWTNMXNmejF7OEG=	NYm4TVhiOjV2OUi1OFI>
BAECs	M1mx[mZ2dmO2aX;uJGF{e2G7	Moi0NVDDqM7:TR?=	M1vXRVHDqGkEoB?=	Mn\PSG1UVw>?	M3XIbIlvcGmkaYTzJJRp\SCrbnPy[YF{\SCrbjDOU3Mh[WO2aY\peJk>	NVjBfpJUOjV2OUi1OFI>
U1242	MnezT4lv[XOnIFHzd4F6	MVqzJO69VcLi	NHW3[4MxNjViaB?=	NUjiPYdpTE2VTx?=	NI\obHLDqGmwaHnibZR{KHSqZTDBWG0hc2mwYYPl	NGLqdXMzOzZ{MESwPS=>
U87	NEHqcG1McW6jc3WgRZN{[Xl?	MUWzJO69VcLi	M2LBd\|AvPSCq	NEnUVXJFVVOR	M1L2SeKhcW6qaXLpeJMhfGinIFHUUUBscW6jc3W=	MnqwNlM3OjB2MEm=
U1242	MmjoRZBweHSxc3nzJGF{e2G7	M3u3VFMh\|ryPwrC=	Ml\VNeKhcMLi	NXvJd5lUTE2VTx?=	NVLUdlA4emGmaX;z[Y5{cXSrenXzJIh2dWGwIHfsbY9u[SClZXzsdy=>	MoXrNlM3OjB2MEm=
U87	NF;FVW9CeG:ydH;zbZMhSXO\|YYm=	MXmzJO69VcLi	Mnm4NeKhcMLi	NWDPd3ZUTE2VTx?=	NH;sfnVz[WSrb4PlcpNqfGm8ZYOgbJVu[W5iZ3zpc41iKGOnbHzz	M33OeFI{PjJyNEC5
U1242	M{OwOmtqdmG\|ZTDBd5NigQ>?	M3vMVFAvODFvMzFOwG3DqA>?	Mk\XNUBp	M1XnTGROW09?	NYGzdXlM[myxY3vzJGFVVSCtaX7hd4Uh[WO2aY\peJkh[XRibH;3JINwdmOnboTyZZRqd26\|	NWDjbG9KOjJ\|N{C0PFU>

... Click to View More Cell Line Experimental Data

In vivo

In orthotopic glioma U1242/luc-GFP xenograft models, the combination of KU-60019 and radiation significantly increases survival of mice than KU-60019 alone, radiation alone, or no treatment. In addition, p53-mutant gliomas is much more sensitive to KU-60019 radiosensitization than wild-type glioma. ^[2]

Protocol

Cell Research:^[1]	+ Expand Cell lines: U87 and U1242 Concentrations: Dissolved in water, final concentrations ~3 μM Incubation Time: 1, 3, and 5 days Method: Cells are exposed to KU-60019 for 1, 3, and 5 days. Cell growth is determined by AlamarBlue. AlamarBlue is added to the medium to the recommended final concentration. Plates are incubated for 1 hour at 37 °C, fluorescence is determined on a Fluoro-Count plate reader (excitation 530 nm, emission 590 nm), and values are taken as a measure of cell growth. Cell survival is determined by trypan blue/fluorescence activated cell sorting (FACS) assay. (Only for Reference)
Animal Research:^[2]	+ Expand Animal Models: Athymic female mice harboring orthotopic glioma U1242/luc-GFP tumors or human glioma U1242/luc-GFP tumors Formulation: PBS Dosages: KU-60019 (10 μM) is delivered at a rate of 0.5 μL/h by osmotic pump; KU-60019 (250 μM) in 12.5 μL is infused by CED. Administration: Administered intratumorally by convection-enhanced delivery or osmotic pump (Only for Reference)

Cell Research:^[1]

+ Expand

Cell lines: U87 and U1242
Concentrations: Dissolved in water, final concentrations ~3 μM
Incubation Time: 1, 3, and 5 days
Method: Cells are exposed to KU-60019 for 1, 3, and 5 days. Cell growth is determined by AlamarBlue. AlamarBlue is added to the medium to the recommended final concentration. Plates are incubated for 1 hour at 37 °C, fluorescence is determined on a Fluoro-Count plate reader (excitation 530 nm, emission 590 nm), and values are taken as a measure of cell growth. Cell survival is determined by trypan blue/fluorescence activated cell sorting (FACS) assay.
(Only for Reference)

Animal Research:^[2]

+ Expand

Animal Models: Athymic female mice harboring orthotopic glioma U1242/luc-GFP tumors or human glioma U1242/luc-GFP tumors
Formulation: PBS
Dosages: KU-60019 (10 μM) is delivered at a rate of 0.5 μL/h by osmotic pump; KU-60019 (250 μM) in 12.5 μL is infused by CED.
Administration: Administered intratumorally by convection-enhanced delivery or osmotic pump
(Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	18 mg/mL warmed (32.86 mM)
	Water	Insoluble
	Ethanol	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download KU-60019 SDF

Molecular Weight	547.67
Formula	C₃₀H₃₃N₃O₅S
CAS No.	925701-49-1
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A

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ATM/ATR Signaling Pathway Map

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Newest ATM/ATR Inhibitor

VE-822 ^New : ATR inhibitor with IC50 of 19 nM.

Related ATM/ATR Products4

AZD6738 ^New

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CHIR-99021 (CT99021) ^New

CHIR-99021 (CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 of 10 nM and 6.7 nM, respectively. CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs.
Dorsomorphin (Compound C) ^New

Dorsomorphin is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type I BMP receptor activity.
KU-55933 (ATM Kinase Inhibitor)

KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/K_i of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.
VE-821

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Berzosertib (VE-822)

VE-822 is an ATR inhibitor with IC50 of 19 nM in HT29 cells.

Features:VE-822 is a highly selective and potent derivative of the ATR inhibitor VE-821.
Chloroquine Phosphate

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AZ20

AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR.

Features:AZ20 is the first reported inhibitor of ATR protein kinase demonstrating tumor growth inhibition in vivo.
CP-466722

CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells.
ETP-46464

ETP-46464 is a potent and selective inhibitor of ATR with IC50 of 25 nM.

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KU-60019