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MedKoo Cat#: 406441 | Name: KU-60019
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

KU-60019 is a potent and selective ATM inhibitor. KU-60019 is 10-fold more effective than KU-55933 at blocking radiation-induced phosphorylation of key ATM targets in human glioma cells. As expected, KU-60019 is a highly effective radiosensitizer of human glioma cells. KU-60019 inhibits the DNA damage response, reduces AKT phosphorylation and prosurvival signaling, inhibits migration and invasion, and effectively radiosensitizes human glioma cells

Chemical Structure

KU-60019
KU-60019
CAS#925701-46-8

Theoretical Analysis

MedKoo Cat#: 406441

Name: KU-60019

CAS#: 925701-46-8

Chemical Formula: C30H33N3O5S

Exact Mass: 547.2141

Molecular Weight: 547.67

Elemental Analysis: C, 65.79; H, 6.07; N, 7.67; O, 14.61; S, 5.85

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
10mg USD 550.00 2 Weeks
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Related CAS #
No Data
Synonym
KU60019; KU 60019; KU-60019.
IUPAC/Chemical Name
2-((2S,6R)-2,6-dimethylmorpholino)-N-(5-(6-morpholino-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamide.
InChi Key
SCELLOWTHJGVIC-BGYRXZFFSA-N
InChi Code
InChI=1S/C30H33N3O5S/c1-19-16-32(17-20(2)37-19)18-28(35)31-23-6-7-27-22(13-23)12-21-4-3-5-25(30(21)39-27)26-14-24(34)15-29(38-26)33-8-10-36-11-9-33/h3-7,13-15,19-20H,8-12,16-18H2,1-2H3,(H,31,35)/t19-,20+
SMILES Code
O=C(NC1=CC(CC2=C(C(C3=CC(C=C(N4CCOCC4)O3)=O)=CC=C2)S5)=C5C=C1)CN6C[C@H](C)O[C@H](C)C6
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Product Data
Product Data
Instruction
View handling instruction
Biological target:
KU-60019 is an improved ATM kinase-specific inhibitor with IC50 of 6.3 nM.
In vitro activity:
The second generation ATMi analog KU-60019 provided quick, reversible and complete inhibition of the DDR at sub-micromolar concentrations in human glioblastoma cells. KU-60019 inhibited the phosphorylation of the major DNA damage effectors p53, H2AX and KAP1 as well as AKT. Reference: Cell Cycle. 2012 Mar 15;11(6):1167-73. https://pubmed.ncbi.nlm.nih.gov/22370485/
In vivo activity:
Lastly, the ATM inhibitor KU-60019 was specifically toxic to PTEN mutant cancer cells in mouse tumor xenografts and reversible by reintroduction of wild-type PTEN. Reference: Cancer Res. 2015 Jun 1;75(11):2159-65. https://pubmed.ncbi.nlm.nih.gov/25870146/
Solvent mg/mL mM
Solubility
DMF 20.0 36.52
DMF:PBS (pH 7.2) (1:1) 0.5 0.91
DMSO 75.0 136.94
Ethanol 50.0 91.30
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 547.67 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Golding SE, Rosenberg E, Adams BR, Wignarajah S, Beckta JM, O'Connor MJ, Valerie K. Dynamic inhibition of ATM kinase provides a strategy for glioblastoma multiforme radiosensitization and growth control. Cell Cycle. 2012 Mar 15;11(6):1167-73. doi: 10.4161/cc.11.6.19576. Epub 2012 Mar 15. PMID: 22370485; PMCID: PMC3335919. 2. Golding SE, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft XF, Chong WY, Hummersone M, Rigoreau L, Menear KA, O'Connor MJ, Povirk LF, van Meter T, Valerie K. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009 Oct;8(10):2894-902. doi: 10.1158/1535-7163.MCT-09-0519. Epub 2009 Oct 6. PMID: 19808981; PMCID: PMC2761990. 3. McCabe N, Hanna C, Walker SM, Gonda D, Li J, Wikstrom K, Savage KI, Butterworth KT, Chen C, Harkin DP, Prise KM, Kennedy RD. Mechanistic Rationale to Target PTEN-Deficient Tumor Cells with Inhibitors of the DNA Damage Response Kinase ATM. Cancer Res. 2015 Jun 1;75(11):2159-65. doi: 10.1158/0008-5472.CAN-14-3502. Epub 2015 Apr 13. PMID: 25870146.
In vitro protocol:
1. Golding SE, Rosenberg E, Adams BR, Wignarajah S, Beckta JM, O'Connor MJ, Valerie K. Dynamic inhibition of ATM kinase provides a strategy for glioblastoma multiforme radiosensitization and growth control. Cell Cycle. 2012 Mar 15;11(6):1167-73. doi: 10.4161/cc.11.6.19576. Epub 2012 Mar 15. PMID: 22370485; PMCID: PMC3335919. 2. Golding SE, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft XF, Chong WY, Hummersone M, Rigoreau L, Menear KA, O'Connor MJ, Povirk LF, van Meter T, Valerie K. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009 Oct;8(10):2894-902. doi: 10.1158/1535-7163.MCT-09-0519. Epub 2009 Oct 6. PMID: 19808981; PMCID: PMC2761990.
In vivo protocol:
1. McCabe N, Hanna C, Walker SM, Gonda D, Li J, Wikstrom K, Savage KI, Butterworth KT, Chen C, Harkin DP, Prise KM, Kennedy RD. Mechanistic Rationale to Target PTEN-Deficient Tumor Cells with Inhibitors of the DNA Damage Response Kinase ATM. Cancer Res. 2015 Jun 1;75(11):2159-65. doi: 10.1158/0008-5472.CAN-14-3502. Epub 2015 Apr 13. PMID: 25870146.
1: Vecchio D, Daga A, Carra E, Marubbi D, Baio G, Neumaier CE, Vagge S, Corvò R, Pia Brisigotti M, Louis Ravetti J, Zunino A, Poggi A, Mascelli S, Raso A, Frosina G. Predictability, efficacy and safety of radiosensitization of glioblastoma-initiating cells by the ATM inhibitor KU-60019. Int J Cancer. 2013 Dec 19. doi: 10.1002/ijc.28680. [Epub ahead of print] PubMed PMID: 24443327. 2: Zirkin S, Davidovich A, Don J. The PIM-2 kinase is an essential component of the ultraviolet damage response that acts upstream to E2F-1 and ATM. J Biol Chem. 2013 Jul 26;288(30):21770-83. doi: 10.1074/jbc.M113.458851. Epub 2013 Jun 11. PubMed PMID: 23760264; PubMed Central PMCID: PMC3724634. 3: Biddlestone-Thorpe L, Sajjad M, Rosenberg E, Beckta JM, Valerie NC, Tokarz M, Adams BR, Wagner AF, Khalil A, Gilfor D, Golding SE, Deb S, Temesi DG, Lau A, O'Connor MJ, Choe KS, Parada LF, Lim SK, Mukhopadhyay ND, Valerie K. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation. Clin Cancer Res. 2013 Jun 15;19(12):3189-200. doi: 10.1158/1078-0432.CCR-12-3408. Epub 2013 Apr 25. PubMed PMID: 23620409; PubMed Central PMCID: PMC3687028. 4: Golding SE, Rosenberg E, Adams BR, Wignarajah S, Beckta JM, O'Connor MJ, Valerie K. Dynamic inhibition of ATM kinase provides a strategy for glioblastoma multiforme radiosensitization and growth control. Cell Cycle. 2012 Mar 15;11(6):1167-73. doi: 10.4161/cc.11.6.19576. Epub 2012 Mar 15. PubMed PMID: 22370485; PubMed Central PMCID: PMC3335919. 5: Gamper AM, Choi S, Matsumoto Y, Banerjee D, Tomkinson AE, Bakkenist CJ. ATM protein physically and functionally interacts with proliferating cell nuclear antigen to regulate DNA synthesis. J Biol Chem. 2012 Apr 6;287(15):12445-54. doi: 10.1074/jbc.M112.352310. Epub 2012 Feb 23. PubMed PMID: 22362778; PubMed Central PMCID: PMC3320994. 6: Raso A, Vecchio D, Cappelli E, Ropolo M, Poggi A, Nozza P, Biassoni R, Mascelli S, Capra V, Kalfas F, Severi P, Frosina G. Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein. Brain Pathol. 2012 Sep;22(5):677-88. doi: 10.1111/j.1750-3639.2012.00566.x. Epub 2012 Feb 21. PubMed PMID: 22257080. 7: Golding SE, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft XF, Chong WY, Hummersone M, Rigoreau L, Menear KA, O'Connor MJ, Povirk LF, van Meter T, Valerie K. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009 Oct;8(10):2894-902. doi: 10.1158/1535-7163.MCT-09-0519. Epub 2009 Oct 6. PubMed PMID: 19808981; PubMed Central PMCID: PMC2761990.