AT7519 hydrochloride is a multi-CDK inhibitor for CDK1, 2, 4, 6 and 9 with IC50 of 10-210 nM. AT7519 displays potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by [(3)H] Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3beta (GSK-3beta) phosphorylation.
|Cell lines||MM.1S, MM.1R, RPMI8226, U266, RPMI8266, RPMI-Dox40, OPM1 cells, primary MM cells and PBMNCs|
|Preparation method||Incubating cells with different concentrations of AT7519 for 24 or 48 hours at 37°C. Assaying cell viability by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrasodium bromide (MTT) dye absorbance. Measuring DNA synthesis by tritiated thymidine uptake (3H-TdR).Assessing Apoptosis by using Annexin V/PI staining. Defining the percentage of cells undergoing apoptosis as the sum of early apoptosis (Annexin V-positive cells) and late apoptosis (Annexin V-positive and PI-positive cells|
|Concentrations||Dissolved in DMSO at a concentration of 10 mM, final concentrations 0.25-4 μM|
|Incubation time||24 or 48 hoursMale SCID mice inoculated subcutaneously with MM.1S cells|
|Formulation||Dissolved in 0.9% saline|
|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.
Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation.
Alessandri, et al. PLoS One. 2011;6(9):e25683. PMID: 21984938.
A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors.
Mahadevan, et al. Ann Oncol. 2011 Sep;22(9):2137-43. PMID: 21325451.
AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples.
Squires, et al. Mol Cancer Ther. 2010 Apr;9(4):920-8. PMID: 20354122.
AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition.
Santo, et al. Oncogene. 2010 Apr 22;29(16):2325-36. PMID: 20101221.
|Related CDK Products|
NU2058 is a guanine-based CDK inhibitor with IC50 of 17 μM and 26 μM for CDK2 and CDK1.
LDC000067 is a highly selective CDK9 inhibitor with IC50 of 44 nM, 55/125/210/ >227/ >227-fold selectivity over CDK2/1/4/6/7.
RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases.
LDC4297 is a novel CDK7 inhibitor (IC50=0.13±0.06 nM for CDK7 versus IC50s between 10 nM and 10,000 nM for all other analyzed CDKs).
THZ1 is a covalent CDK7 inhibitor which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.