154447-35-5 Usage
Description
NU7026 is a chemical compound that functions as a DNA-dependent protein kinase (DNA-PK) inhibitor. It is known for its antiproliferative properties and is utilized in various experimental applications to study its effects on different cell types and conditions.
Uses
Used in Cancer Research:
NU7026 is used as an antiproliferative agent for studying its effects on cancer cell growth and proliferation. It is particularly useful in understanding the role of DNA-PK in cancer development and progression.
Used in Colon Cancer Cell Studies:
In the field of colon cancer research, NU7026 is used as a DNA-PK inhibitor to pre-treat colon cancer cells in kinase inhibitor experiments. This helps researchers investigate the compound's influence on cell behavior and its potential as a therapeutic agent for colon cancer treatment.
Used in Fertility Studies:
NU7026 is utilized in experiments involving the treatment of zygotes with visible pronuclei post 20 hours of human chorionic gonadotropin (hCG) administration. This application aids in understanding the compound's impact on early-stage embryonic development and its potential implications for fertility treatments.
Used in Hepatotoxicity Studies:
In the context of hepatotoxicity research, NU7026 is used to determine its influence on the cytotoxicity of dibenzo[def,p]chrysene on HepG2 cells. This application helps researchers explore the compound's potential role in mitigating or exacerbating liver cell damage caused by toxic substances.
Overall, NU7026 is a versatile compound with applications in various fields, including cancer research, fertility studies, and hepatotoxicity investigations. Its use as a DNA-PK inhibitor allows researchers to explore its potential therapeutic effects and better understand the underlying mechanisms of various diseases and conditions.
Biological Activity
ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK). Displays selectivity over other PIKK family enzymes (IC 50 values are 0.23, 13.0, > 100 and > 100 μ M for DNA-PK, PI3K, ATM and ATR respectively). Radiosensitizes both proliferating and quiescent mouse embryonic fibroblast cells to IR and inhibits DSB repair.
Biochem/physiol Actions
Cell permeable, small molecule benzochromenone inhibitor of DNA-PK (DNA dependent protein kinase).
Check Digit Verification of cas no
The CAS Registry Mumber 154447-35-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,4,4,4 and 7 respectively; the second part has 2 digits, 3 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 154447-35:
(8*1)+(7*5)+(6*4)+(5*4)+(4*4)+(3*7)+(2*3)+(1*5)=135
135 % 10 = 5
So 154447-35-5 is a valid CAS Registry Number.
InChI:InChI=1/C17H15NO3/c19-15-11-16(18-7-9-20-10-8-18)21-17-13-4-2-1-3-12(13)5-6-14(15)17/h1-6,11H,7-10H2
154447-35-5Relevant articles and documents
Selective benzopyranone and pyrimido[2,1-α]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: Synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro
Griffin, Roger J.,Fontana, Gabriele,Golding, Bernard T.,Guiard, Sophie,Hardcastle, Ian R.,Leahy, Justin J. J.,Martin, Niall,Richardson, Caroline,Rigoreau, Laurent,Stockley, Martin,Smith, Graeme C. M.
, p. 569 - 585 (2007/10/03)
A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4- one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inhibitory activity varied widely over the series of compounds evaluated (IC50 values ranged from 0.19 to >10 μM), with excellent activity being observed for the 7,8-benzochromen-4-one and pyrimido[2,1-a] isoquinolin-4-one templates. By contrast, inhibitors based on the benzochromen-2-one (coumarin) or 2-aryl-7,8-benzochromen-4-one (flavone) scaffolds were less potent. Crucially, these studies revealed a very constrained structure-activity relationship at the 2-position of the benzopyranone and pyrimido[2,1-a]-isoquinolin-4-one pharmacophore, with only a 2-morpholino or 2-(2′-methylmorpholino) group being tolerated at this position. More detailed biological studies conducted with the most potent inhibitor NU7163 (48; IC50 = 0.19 μM) demonstrated ATP-competitive DNA-PK inhibition, with a Ki value of 24 nM, and 48 exhibited selectivity for DNA-PK compared with the related enzymes ATM, ATR, mTOR, and PI 3-K (p110alpha). Compound 48 sensitized the HeLa human tumor cell line to the cytotoxic effects of ionizing radiation in vitro, a dose modification factor of 2.3 at 10% survival being observed with an inhibitor concentration of 5 μM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.
