AT7519

SKU: orb1300982

Description

AT7519

Research Area

Cell Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 844442-38-2
• MW: 382.24
• Purity: 99.67%
• Formula: C₁₆H₁₇Cl₂N₅O₂
• SMILES: N(C(=O)C1=C(Cl)C=CC=C1Cl)C=2C(C(NC3CCNCC3)=O)=NNC2
• Target: Apoptosis,CDK,GSK-3
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.23 mM);DMSO:16.67 mg/mL (43.61 mM)

Bioactivity

• Target IC50:
  CDK9-CyclinT:10 nM|CDK2-CyclinA:47 nM|CDK7-CyclinH-MAT1:2400 nM|CDK1-CyclinB:210 nM|GSK-3β:89 nM|CDK6-CyclinD3:170 nM|Cdk4-CyclinD1:100 nM|CDK5-p35:13 nM
• In Vivo:
  A twice daily dosing of AT7519 (9.1 mg/kg) causes tumor regression of both early-stage and advanced-stage s.c. tumors in the HCT116 and HT29 colon cancer xenograft models. AT7519 treatment (15 mg/kg) inhibits tumor growth and prolong the median ove All survival of mice in the human mM xenograft mouse model in association with increased caspase 3 activation.
• In Vitro:
  AT7519 is an ATP competitive CDK inhibitor with a Ki value of 38 nM for CDK1. AT7519 is inactive against All non-CDK kinases wit the exception of GSK3β IC50 = 89 nM). AT7519 shows potent ant Proliferative activity in a variety of human tumor cell lines with IC50 Values ranging from 40 nM for MCF-7 to 940 nM for SW620 consistent wit the Inhibition of CDK1 and CDK2. AT7519 induces dose-dependent cytotoxicity in multiple myeloma (MM) cell lines with IC50 Values ranging from 0.5 to 2 μM at 48 hours, wit the most sensitive cell lines being MM.1S (0.5 μM) and U266 (0.5 μM) an the most resistant MM.1R (>2 μM). It does not induce cytotoxicity in peripheral blood mononuclear cells (PBMNC). AT7519 partially overcome the Proliferative advantage conferred by IL6 and IGF-1 as well a the Protective effect of bone marrow stromal cells (BMSCs). AT7519 induces rapid dephosphorylation of RNA pol II CTD at serine 2 and serine 5 sites, and leads to the Inhibition of transcription, partially contributing to AT7519 induced cytotoxicity of mM cells. AT7519 induces activation of GSK-3β by down-regulating GSK-3β phosphorylation, which also contributes to AT7519 induced apoptosis independent o the Inhibition of transcription.
• Cell Research:
  Cells are incubated with different concentration of AT7519 for 24 or 48 hours at 37℃. Cell viability 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). Apoptosis is assessed by using Annexin V/PI staining the percentage of cells undergoing apoptosis is defined a the sum of early apoptosis (Annexin V-positive cells) and late apoptosis (Annexin V-positive and PI-positive cells(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Cyclin dependent kinase, CDK, CDK2/CyclinA, CDK5/p35, CDK4/CyclinD1, CDK9/CyclinT, AT7519, AT-7519, AT7519M, AT 7519, Apoptosis, GSK-3β, GSK3, Inhibitor, inhibit

Compound Identifiers

PubChem CID

11338033