KU-60019-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEKU-60019Cat. No.: HY-12061CAS No.: 925701-46-8分式: CHNOS分量: 547.67作靶點: ATM/ATR作通路: Cell Cycle/DNA Damage; PI3K/Akt/mTOR儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 30 mg/mL (54.78 mM)* me

2、ans soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.8259 mL 9.1296 mL 18.2592 mL5 mM 0.3652 mL 1.8259 mL 3.6518 mL10 mM 0.1826 mL 0.9130 mL 1.8259 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 KU-60019種 ATM 激酶特異性的抑制劑，IC50 為 6.3 nM。IC50 & Ta

3、rget ATM DNA-PKcs6.3 nM (IC50) 1.7 M (IC50)體外研究KU-60019 is an improved analogue of KU-55933. KU-55933 has an IC50 of 13 nM and Ki of 2.2 nM in vitro1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEand is highly specific for the ATM kinase using a panel of 60 protein kinases. KU-60019 is an improvedi

4、nhibitor of the ATM kinase with an IC50 of 6.3 nM, approximately half that of KU-55933. The IC50 values forDNA-PKcs and ATR are 1.7 and 10 M, 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

5、key ATMtargets in human glioma cells. In human U87 glioma cells, KU-55933 completely inhibits phosphorylation ofp53 (S15) at 10 M but not at 3 M, whereas -H2AX levels are only partly reduced with 10 M 1 h afterirradiation. By comparison, 3 M KU-60019 completely inhibits p53 phosphorylation and parti

6、al inhibits at 1 M 1.體內(nèi)研究 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 growthinhibition is especially evident at the start of the experiment

7、(days 5-12) just after KU-60019 is administered(days 1-5) 2.PROTOCOLCell Assay 1 Cell growth is determined by AlamarBlue. U1242 cells are serially diluted, allowed to attach for 6 h and thenexposed to KU-60019 at 3 M. At days 1, 3 and 5 after seeding, AlamarBlue is added to the medium to therecommen

8、ded final concentration. Plates are incubated for 1 h at 37C and fluorescence determined on aFluoroCount plate reader (excitation 530 nm, emission 590 nm) and values taken as a measure of cellgrowth 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Anim

9、al Mice 2Administration 2 Cells (3107) 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 48hours up to removal of the animal from the experiment. Forty-eight hours after P

10、TEN induction, animals areadministered KU-60019 (100 mg/kg) for 5 consecutive days and measured until they reach a target 400 mm3volume. Measurements of tumor volume and body weight took place every 3 days using calipers.MCE has not independently confirmed the accuracy of these methods. They are for

11、 reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. J Mol Med (Berl). 2019 Jun 14. Neoplasia. 2018 Mar 28;20(5):478-488. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChem

12、E1. Golding SE, et al. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvivalsignaling, 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 KinaseATM. Cancer Res. 2015 Jun 1;75(11):2159-65.McePdfHeightCauti