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KU-60019

Name: KU-60019
Brand: Selleck Chemicals
SKU: S1570
Rating: 5 (146 reviews)

Catalog No.S1570 Purity:99.78%

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.

KU-60019 Chemical Structure

CAS No. 925701-49-1

Purity & Quality Control

Batch: Purity: 99.78%

99.78

KU-60019 Related Products

Related Targets	ATM ATR	Click to Expand
Related Products	KU-55933 VE-821 Berzosertib (VE-822) Ceralasertib (AZD6738) AZ20 AZD0156 Mirin AZD1390 CP-466722 Elimusertib (BAY-1895344) hydrochloride ETP-46464 Elimusertib (BAY-1895344) CGK 733 VX-803 (M4344) AZ31 AZ32 HAMNO	Click to Expand
Related Compound Libraries	FDA-approved Drug Library Natural Product Library Apoptosis Compound Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	Click to Expand

Signaling Pathway

ATM/ATR Signaling Pathway

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
BAECs	Function Assay	10 μM	1 h	DMSO	abolishes the phosphorylation of ATM-Ser1981	25498542
BAECs	Function Assay	10 μM	1 h	DMSO	inhibits the increase in NOS activity	25498542
U1242	Kinase Assay	3 μM	0.5 h	DMSO	inhibits the ATM kinase	23620409
U87	Kinase Assay	3 μM	0.5 h	DMSO	inhibits the ATM kinase	23620409
U1242	Apoptosis Assay	3 μM	1 h	DMSO	radiosensitizes human glioma cells	23620409
U87	Apoptosis Assay	3 μM	1 h	DMSO	radiosensitizes human glioma cells	23620409
U1242	Kinase Assay	0.01-3 μM	1 h	DMSO	blocks ATM kinase activity at low concentrations	22370485
glioma	Function assay				Inhibition of ATM kinase in human glioma cells, IC50 = 0.006 μM.	25387153
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
Click to View More Cell Line Experimental Data

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
In vitro	Compared to KU-55933, KU-60019 is an improved 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 Research	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.
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	p-ATM / ATM / p-AKT / AKT / PKM2		30799198
	Immunofluorescence	GLUT1		30799198

In Vivo
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]
Animal Research	Animal Models	Athymic female mice harboring orthotopic glioma U1242/luc-GFP tumors or human glioma U1242/luc-GFP tumors
	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

References

Chemical Information & Solubility

Molecular Weight	547.67	Formula	C₃₀H₃₃N₃O₅S
CAS No.	925701-49-1	SDF	Download KU-60019 SDF
Smiles	CC1CN(CC(O1)C)CC(=O)NC2=CC3=C(C=C2)SC4=C(C3)C=CC=C4C5=CC(=O)C=C(O5)N6CCOCC6
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (182.59 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.13mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

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Frequently Asked Questions

Question 1:
what vehicle do you recommend for in vivo use of this compound?

Answer:
The formula for i.p. injections: 5% stock solution (100mg/ml) +30% PEG 300+ddH2O could reach a final concentration of 5mg/ml.

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