[CAS NO. 844442-38-2] AT7519
PRODUCTS SPECIFICATIONS [844442-38-2]
DESCRIPTION [844442-38-2]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 382.24 |
| Molecular Formula | C16H17Cl2N5O2 |
| SMILES | O=C(NC1=CNN=C1C(NC2CCNCC2)=O)C3=C(Cl)C=CC=C3Cl |
7 Publications Citing Use of MCE
Summary
IC50 & Target
|
CDK9/Cyclin T 10 nM (IC 50 ) |
CDK5/p35 13 nM (IC 50 ) |
cdk2/cyclin A 47 nM (IC 50 ) |
Cdk4/cyclin D1 100 nM (IC 50 ) |
cdk6/cyclin D3 170 nM (IC 50 ) |
||
|
Cdk1/cyclin B 210 nM (IC 50 ) |
CDK7/Cyclin H/MAT1 2400 nM (IC 50 ) |
GSK3β 89 nM (IC 50 ) |
||||
In Vitro
AT7519 (0-4 μM) results in dose-dependent cytotoxicity with IC 50 s ranging from 0.5 to 2 μM in MM cells, and this induced cytotoxicity is associated with GSK-3β activation independent of transcriptional inhibition. AT7519 overcomes proliferative advantage conferred by cytokines and the protective effect of BMSC. AT7519 (0.5 μM) induces apoptosis of MM cells in a time-dependent manner. Moreover, AT7519 (0.5 μM) inhibits phosphorylation of RNA polymerase II CTD and partially inhibits RNA synthesis in MM.1S cells [1] . AT7519 (250 nM) inhibits cell cycle progression in human tumor cell lines. AT7519 also induces apoptosis of human tumor cell lines [2] . AT7519 (100-700 nM) induces apoptosis in leukemia cell lines. AT7519 also inhibits transcription in human tumor cell lines. Furthermore, AT7519 inhibits RNA polymerase II and reduces antiapoptotic protein levels [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
AT7519 inhibits tumor growth in a human MM xenograft mouse model [1] . AT7519 (4.6 and 9.1 mg/kg/dose) inhibits the growth of early-stage HCT116 tumor xenografts. AT7519 (10 mg/kg, i.p.) also inhibits the target CDKs in HCT116 tumor-bearing BALB/c nude mice [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01183949 | Astex Pharmaceuticals, Inc.|Multiple Myeloma Research Consortium |
Multiple Myeloma
|
November 2010 | Phase 1|Phase 2 |
| NCT00390117 | NCIC Clinical Trials Group|Canadian Cancer Trials Group |
Lymphoma|Unspecified Adult Solid Tumor, Protocol Specific
|
August 22, 2006 | Phase 1 |
| NCT01652144 | NCIC Clinical Trials Group|Astex Pharmaceuticals, Inc.|Canadian Cancer Trials Group |
Mantle Cell Lymphoma
|
July 24, 2012 | Phase 2 |
| NCT01627054 | NCIC Clinical Trials Group|Astex Pharmaceuticals, Inc.|Canadian Cancer Trials Group |
Chronic Lymphocytic Leukemia
|
June 21, 2012 | Phase 2 |
| NCT02503709 | National Cancer Institute (NCI) |
Advanced Malignant Solid Neoplasm|Metastatic Malignant Solid Neoplasm|Unresectable Solid Neoplasm
|
April 8, 2016 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 50 mg/mL ( 130.81 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6162 mL | 13.0808 mL | 26.1616 mL |
| 5 mM | 0.5232 mL | 2.6162 mL | 5.2323 mL |
| 10 mM | 0.2616 mL | 1.3081 mL | 2.6162 mL |
References
- [1] Santo L, et al. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36.
- [2] Squires MS, et al. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.
- [3] Squires MS, et al. AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. Mol Cancer Ther. 2010 Apr;9(4):920-8.
Synonyms