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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 Experiment | |
|---|---|
| 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 |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | Dissolved in 0.9% saline |
| Dosages | 15 mg/kg/day |
| Administration | Dosed i.p. |
| Molecular Weight | 418.71 |
| Formula | C16H18Cl3N5O2 |
| CAS Number | 902135-91-5 |
| Solubility (25°C) | DMSO 50 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related CDK Products |
|---|
| (E/Z)-Zotiraciclib citrate
(E/Z)-Zotiraciclib citrate is a potent CDK2, JAK2, and FLT3 inhibitor. |
| Abemaciclib metabolites M2
Abemaciclib metabolite M2 (LSN2839567) is a metabolite of Abemaciclib, acts as a potent CDK4 and CDK6 inhibitor, with IC50 values of 1.2 and 1.3 nM, respectively. |
| CDK9-IN-1
CDK9-IN-1 is a novel, selective CDK9 inhibitor, with an IC50 of 39 nM for CDK9/CycT1, it can be used for the research of HIV infection. |
| XO44
XO44 (PF-6808472) is a broad-spectrum covalent kinase probe. |
| ML 315
ML 315 is a selective dual inhibitor of CDK and DYRK with IC50s of 68 nM and 282 nM, respectively. |
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