DC Chemicals Limited
China
Product Name: KU-60019
Price: $600.0/100mg $1100.0/250mg $2200.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

925701-46-8

925701-46-8 structure

925701-46-8 structure

Name: KU 60019
Chemical Name: ku-60019
CAS Number: 925701-46-8
Molecular Formula: C₃₀H₃₃N₃O₅S
Molecular Weight: 547.665
Catalog: Signaling Pathways Cell Cycle/DNA Damage ATM/ATR
Create Date: 2017-07-04 15:19:41
Modify Date: 2024-01-10 21:30:15
KU-60019 is an improved ATM kinase-specific inhibitor with IC50 of 6.3 nM.

Name	ku-60019
Synonyms	2-[(2R,6S)-2,6-Dimethyl-4-morpholinyl]-N-{5-[6-(4-morpholinyl)-4-oxo-4H-pyran-2-yl]-9H-thioxanthen-2-yl}acetamide 4-Morpholineacetamide, 2,6-dimethyl-N-[5-[6-(4-morpholinyl)-4-oxo-4H-pyran-2-yl]-9H-thioxanthen-2-yl]-, (2R,6S)-

Description	KU-60019 is an improved ATM kinase-specific inhibitor with IC50 of 6.3 nM.
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> ATM/ATR Signaling Pathways >> PI3K/Akt/mTOR >> ATM/ATR Research Areas >> Cancer
Target	ATM:6.3 nM (IC50) DNA-PKcs:1.7 μM (IC50)
In Vitro	KU-60019 is an improved analogue of KU-55933. KU-55933 has an IC50 of 13 nM and Ki of 2.2 nM in vitro and is highly specific for the ATM kinase using a panel of 60 protein kinases. KU-60019 is an improved inhibitor of the ATM kinase with an IC50 of 6.3 nM, approximately half that of KU-55933. The IC50 values for DNA-PKcs and ATR are 1.7 and >10 μM, respectively, almost 270-and 1600-fold higher than for ATM. KU-60019 is 10-fold more effective than KU-55933 at blocking radiation-induced phosphorylation of key ATM targets in human glioma cells. In human U87 glioma cells, KU-55933 completely inhibits phosphorylation of p53 (S15) at 10 μM but not at 3 μM, whereas γ-H2AX levels are only partly reduced with 10 μM 1 h after irradiation. By comparison, 3 μM KU-60019 completely inhibits p53 phosphorylation and partial inhibits at 1 μM[1].
In Vivo	Despite PTEN-deficient control tumors reaching a 4-fold increase in size before PTEN wild-type controls, KU-60019-treated PTEN-deficient tumors display a statistically significant slowing in growth. This growth inhibition is especially evident at the start of the experiment (days 5-12) just after KU-60019 is administered (days 1-5)[2].
Cell Assay	Cell growth is determined by AlamarBlue. U1242 cells are serially diluted, allowed to attach for 6 h and then exposed to KU-60019 at 3 μM. At days 1, 3 and 5 after seeding, AlamarBlue is added to the medium to the recommended final concentration. Plates are incubated for 1 h at 37°C and fluorescence determined on a FluoroCount plate reader (excitation 530 nm, emission 590 nm) and values taken as a measure of cell growth[1].
Animal Admin	Mice[2] Cells (3×107) are implanted into male Fox Chase Severe Combined Immunodeficiency (SCID) mice. Administration of Doxycycline is started when tumors reach 100 mm3 in volume and is performed every 48 hours up to removal of the animal from the experiment. Forty-eight hours after PTEN induction, animals are administered KU-60019 (100 mg/kg) for 5 consecutive days and measured until they reach a target 400 mm3 volume. Measurements of tumor volume and body weight took place every 3 days using calipers.
References	[1]. Golding SE, et al. 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. [2]. McCabe N, et al. 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.

Density	1.3±0.1 g/cm3
Boiling Point	786.6±60.0 °C at 760 mmHg
Molecular Formula	C₃₀H₃₃N₃O₅S
Molecular Weight	547.665
Flash Point	429.5±32.9 °C
Exact Mass	547.214111
PSA	109.55000
LogP	5.90
Vapour Pressure	0.0±2.7 mmHg at 25°C
Index of Refraction	1.645