AT7519 Hydrochloride

SKU: orb1307462

Description

AT7519 HCl is a potent, cell-permeable inhibitor targeting multiple cyclin-dependent kinases (CDKs), including CDK1, CDK2, CDK4, CDK6, and CDK9. It is widely used in biochemical and cellular research to study cell cycle progression and transcriptional regulation, demonstrating antitumor activity in both in vitro and in vivo cancer models.

Research Area

Cell Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 902135-91-5
• MW: 418.71
• Purity: 99.90%
• Formula: C₁₆H₁₈Cl₃N₅O₂
• SMILES: Cl.Clc1cccc(Cl)c1C(=O)Nc1c[nH]nc1C(=O)NC1CCNCC1
• Target: GSK-3,Apoptosis,CDK
• Solubility: DMSO:40 mg/mL (95.53 mM);Ethanol:28 mg/mL (66.87 mM);H2O:1 mg/mL (2.39 mM)

Bioactivity

• Target IC50:
  CDK5-p35:13 nM|CDK6-CyclinD3:170 nM|CDK4-CyclinD1:100 nM|CDK2-CyclinA:47 nM|CDK1-CyclinB:210 nM|CDK9-CyclinT:<10 nM|CDK7-CyclinH-MAT1:2400 nM|GSK-3β:89 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 prolongs the median overall 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 with the exception of GSK3β (IC50 = 89 nM). AT7519 shows potent antiproliferative 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 with 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, with the most sensitive cell lines being MM.1S (0.5 μM) and U266 (0.5 μM) and the most resistant MM.1R (>2 μM). It does not induce cytotoxicity in peripheral blood mononuclear cells (PBMNC). AT7519 partially overcomes the proliferative advantage conferred by IL6 and IGF-1 as well as 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 of the inhibition of transcription.
• Cell Research:
  Cells are incubated with different concentrations of AT7519 for 24 or 48 hours at 37°C. 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 as 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.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

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

Compound Identifiers

PubChem CID

25033099