ETP-46464 is a potent inhibitor against mTOR, ATR, DNA-PK, PI 3-Kα and ATM with IC50 of 0.6, 14, 36, 170 and 545 nM, respectively. ETP-46464 preferentially suppresses radiation-induced cellular ATR activity (>90% at 500 nM) over ATM or DNA-PK activity (IC50 > 5 μM) in U2OS cells, while exhibiting much reduced or little potency toward a panel of 26 other kinases (>55% inhibition at 5 μM). ETP-46464 (10 μM) inhibited the UV-induced phosphorylation of CHK1 serine 317. Further, the phosphorylation of ATM serine 1981 was increased in cells incubated in 10 μM ETP-46464 and exposed to 10 J/m2 UV.
|Cell lines||23T, 239T, Calu6 and H460 cells line|
|Preparation method||Proliferation assays MTT Assay (Trevigen, Gaithersburg, MD) was used to measure cell proliferation. Drug combinations were evaluated using CalcuSyn (BIOSOFT, Ferguson, MO) software based on the multiple drug effect equation of Chou-Talalay. Experimental values were imputed into Calcusyn to calculate IC50 and a combination index (CI, a quantitative measure of the synergy (CI < 1), additivity (CI = 1), or antagonism (CI > 1) between drugs). Log-transformed CI’s are plotted against growth inhibition/effective dose (ED) with corresponding 95 % confidence intervals. Synergism is indicated when the 95 % CI falls below the x-axis (log CI = 0; CI = 1), whereas antagonism is indicated when the 95 % CI falls above the x-axis, at each respective region of the effective dose.|
|Incubation time||2 days|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 10 mg/mL|
CGK733 does not inhibit ATM or ATR kinase activity in H460 human lung cancer cells.
Choi S, et al. DNA Repair (Amst). 2011 Oct 10;10(10):1000-2. PMID: 21865098.
A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations.
Toledo LI, et al. Nat Struct Mol Biol. 2011 Jun;18(6):721-7. PMID: 21552262.
|Related ATM/ATR Products|
Identification of potent, highly selective and orally available ATR inhibitor BAY 1895344 with favorable PK properties and promising efficacy in monotherapy and combination in preclinical tumor models
Mirin is a potent Mre11–Rad50–Nbs1 (MRN) complex inhibitor, and inhibits Mre11-associated exonuclease activity.
Candesartan Cilexetil is a specific nonpeptide Ang II receptor (ATR) antagonist and the procompound of candesartan which is an ATR antagonist with an IC50 of 15 μg/kg.
VE-822 is an ATR inhibitor with IC50 of 19 nM.
CGK 733 is a potent and selective inhibitor of ATM/ATR with IC50 of ~200 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.