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  • Product Name: AT7519
  • Price: $300.0/100mg $600.0/250mg $1200.0/1g
  • Purity: 98.0%
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844442-38-2

844442-38-2 structure
844442-38-2 structure
  • Name: AT7519
  • Chemical Name: 4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide
  • CAS Number: 844442-38-2
  • Molecular Formula: C16H17Cl2N5O2
  • Molecular Weight: 382.245
  • Catalog: Biochemical Inhibitor Cell Cycle CDK inhibitor
  • Create Date: 2018-09-01 11:36:01
  • Modify Date: 2024-01-02 17:14:38
  • AT7519 as a potent inhibitor of CDKs, with IC50s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively.
Name 4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide
Synonyms 1H-Pyrazole-3-carboxamide, 4-[(2,6-dichlorobenzoyl)amino]-N-4-piperidinyl-
4-[(2,6-Dichlorobenzoyl)amino]-N-(4-piperidinyl)-1H-pyrazole-3-carboxamide
UNII-X1BF92PW9T
AT 7519
AT7519
cc-301
Description AT7519 as a potent inhibitor of CDKs, with IC50s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively.
Related Catalog
Target

CDK9/Cyclin T:10 nM (IC50)

CDK5/p35:13 nM (IC50)

cdk2/cyclin A:47 nM (IC50)

Cdk4/cyclin D1:100 nM (IC50)

cdk6/cyclin D3:170 nM (IC50)

Cdk1/cyclin B:210 nM (IC50)

CDK7/Cyclin H/MAT1:2400 nM (IC50)

GSK3β:89 nM (IC50)

In Vitro AT7519 (0-4 μM) results in dose-dependent cytotoxicity with IC50s 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].
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].
Cell Assay AT7519's effects on viability of MM cell lines, primary MM cells, and PBMNCs is assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrasodium bromide (MTT) dye absorbance. DNA synthesis is measured by tritiated thymidine uptake (3H-TdR). MM cells (2-3 × 104 cells/well) are incubated in 96-well culture plates with media and different concentrations of AT7519 and/or recombinant IL-6 (10 ng/mL) or IGF-1 (50 ng/mL) for 24 or 48 h at 37°C and 3H-TdR incorporation is measured.
Animal Admin To evaluate the in vivo anti-MM activity of AT7519, male SCID mice are inoculated subcutaneously with 5×106 MM.1S cells in 100 μL serum-free RPMI 1640 medium. When tumors are measurable, mice are treated intraperitoneally (IP) with vehicle or AT7519 dissolved in saline 0.9%. The first group of 10 mice is treated with 15 mg/kg once a day for five days for 2 weeks, and the second group is treated with 15 mg/kg once a day three times a week for four consecutive weeks. The control group receives the carrier alone at the same schedule. Tumor size is measured every alternate day in 2 dimensions using calipers, and tumor volume is calculated with the formula: V= 0.5 a × b2 (a= long diameter of the tumor, b= short diameter of the tumor). Animals are sacrificed when the tumor reaches 2 cm3 or when the tumor is ulcerated. Survival and tumor growth are evaluated from the first day of treatment until death.
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.
Density 1.5±0.1 g/cm3
Boiling Point 586.0±50.0 °C at 760 mmHg
Molecular Formula C16H17Cl2N5O2
Molecular Weight 382.245
Flash Point 308.2±30.1 °C
Exact Mass 381.075928
PSA 102.40000
LogP 0.95
Vapour Pressure 0.0±1.6 mmHg at 25°C
Index of Refraction 1.654
Storage condition -20°C
844443-90-9 structure

844443-90-9

~%

844442-38-2 structure

844442-38-2

Literature: WO2008/1101 A2, ; Page/Page column 329-330 ;
Precursor  1

DownStream  0


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title: CAS No. 844442-38-2 | Chemsrc address: https://www.chemsrc.com/en/baike/1196848.html

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