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AT7519 Hydrochloride

In stock
Catalog No.
A3197
Multi-CDK inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$86.00
In stock
5mg
$78.00
In stock
10mg
$117.00
In stock
50mg
$247.00
In stock
100mg
$325.00
In stock

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Background

IC50: AT7519 showed potent antiproliferative activity (40-940 nmol/L) in a panel of human tumor cell lines.
Cyclin-dependent kinases (CDK) play a central role in the growth, division, and death of eukaryotic cell. This crucial role in cell cycle progression and their deregulation in several human cancers make them attractive therapeutic oncology targets. Series of CDK inhibitors was developed, among which, AT7519 is in early-phase clinical development currently.
In vitro: AT7519 showed potent antiproliferative activity (40-940 nmol/L)in a panel of human tumor cells, and the mechanism of action was shown to be consistent with the inhibition of CDK1 and CDK2. Cell cycle arrest caused by AT7519 followed by apoptosis in human tumor cells and inhibited tumor growth in human tumor xenograft models [1].
In vivo: Tumor regression was observed following twice daily dosing of AT7519 in the HCT116 and HT29 colon cancer xenograft models. The authors show that these effects are linked to inhibition of CDKs in vivo and that AT7519 induces tumor cell apoptosis [1].
Clinical trial: A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors. Electrocardiogram review suggested a dose-dependent increase in QTc and recruitment was discontinued without establishing a maximum tolerated dose. 4 patients with stable disease for >6 months and one had a prolonged partial response. Pharmacokinetic profile indicated modest interpatient variation with linear exposure at increased doses. AT7519 elicited clinical and PD activity resulting from CDK inhibition at doses below the appearance of DLT of QTc prolongation [2].
References:
[1] Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT.Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009;8(2):324-32.
[2] Mahadevan D, Plummer R, Squires MS, Rensvold D, Kurtin S, Pretzinger C, Dragovich T, Adams J, Lock V, Smith DM, Von Hoff D, Calvert H. A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors. Ann Oncol. 2011;22(9):2137-43.

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at -20°C
M.Wt418.71
Cas No.902135-91-5
FormulaC16H18Cl3N5O2
SynonymsAT 7519 Hydrochloride;AT-7519 Hydrochloride
Solubility≥43.3 mg/mL in DMSO with ultrasonic, ≥8.82 mg/mL in EtOH with ultrasonic, ≥29.93 mg/mL in H2O
Chemical Name4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide;hydrochloride
SDFDownload SDF
Canonical SMILESC1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl.Cl
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

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