AT7519

Catalog No.S1524 Batch:S152401

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Technical Data

Formula

C16H17Cl2N5O2
Molecular Weight 382.24 CAS No. 844442-38-2
Solubility (25°C)* In vitro DMSO 10 mg/mL (26.16 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description AT7519 is a multi-CDK inhibitor for CDK1, 2, 4, 6 and 9 with IC50 of 10-210 nM. It is less potent to CDK3 and little active to CDK7. This compound also decrease GSK3β phosphorylation. It induces apoptosis. Phase 2.
Targets
CDK9/CyclinT [1]
(Cell-free assay)		 CDK5/p35 [1]
(Cell-free assay)		 CDK2/CyclinA [1]
(Cell-free assay)		 GSK-3β [1]
(Cell-free assay)		 CDK4/CyclinD1 [1]
(Cell-free assay)		 View More
<10 nM 13 nM 47 nM 89 nM 100 nM
In vitro AT7519 is an ATP competitive CDK inhibitor with a Ki value of 38 nM for CDK1. This compound is inactive against all non-CDK kinases with the exception of GSK3β (IC50 = 89 nM). It 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. [1] This chemical 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). This inhibitor partially overcomes the proliferative advantage conferred by IL6 and IGF-1 as well as the protective effect of bone marrow stromal cells (BMSCs). It 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 its induced cytotoxicity of MM cells. This agent induces activation of GSK-3β by down-regulating GSK-3β phosphorylation, which also contributes to its induced apoptosis independent of the inhibition of transcription. [2]
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. [1] This compound 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. [2]

Protocol (from reference)

Kinase Assay:[1]
  • In vitro Kinase Assays

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Cell Assay:[2]
  • Cell lines

    MM.1S, MM.1R, RPMI8226, U266, RPMI8266, RPMI-Dox40, OPM1 cells, primary MM cells and PBMNCs

  • Concentrations

    Dissolved in DMSO at a concentration of 10 mM, final concentrations 0.25-4 μM

  • Incubation Time

    24 or 48 hours

  • Method

    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).
Animal Study:[2]
  • Animal Models

    Male SCID mice inoculated subcutaneously with MM.1S cells

  • Dosages

    15 mg/kg/day

  • Administration

    Dosed i.p.

References

  • https://pubmed.ncbi.nlm.nih.gov/19174555/
  • https://pubmed.ncbi.nlm.nih.gov/20101221/

Customer Product Validation

Lysates of MDM treated with five-fold dilutions of the indicated compounds (starting concentration: AT7519, 0.5 mmol/l, roscovitine 4 mmol/l) were subjected to SDS-PAGE, transferred, and immunoblotted with antiphopho-SAMHD1, anti-SAMHD1 and anti-Hsp90 antibodies. MDM, monocyte-derived macrophage; SAMHD1, sterile a motif and HD domain-containing protein-1; SD, standard deviation.

Data from [ AIDS , 2014 , 28(15), 2213-22 ]

AT7519 drives eosinophil apoptosis and subsequent clearance by macrophages as assessed by morphological analysis. Representative images from vehicle (E) and AT7519 treated (F) animals are shown (Magnification x400 (i) and x1000 (ii and iii)). In vehicle treated animals (E), black arrows indicate healthy, viable eosinophils while in AT7519-treated animals (F), black arrows indicate typically apoptotic eosinophils and white arrows apoptotic cells inside macrophages.

Data from [ PLoS One , 2011 , 6(9), e25683 ]

<p>U87MG astroglioma cells were loaded with CFSE (5 μM) and treated with 0-400 nM of AT7519. Data acquired on day 0 and day 3 on a FACS Caliber flow cytometer and analysed by FlowJo. Results indicated that AT7519 partially inhibited cell proliferation. Higher than 400 nM resulted in cell death.</p>

, , Dr. Srinivas Narasipura of Rush University Medical Center

Selleck's AT7519 Has Been Cited by 55 Publications

Molecular glues that inhibit deubiquitylase activity and inflammatory signaling [ Nat Struct Mol Biol, 2025, 10.1038/s41594-025-01517-5] PubMed: 40097626
Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer [ Cell Rep Med, 2025, S2666-3791(25)00231-9] PubMed: 40449480
A Huluwa phosphorylation switch regulates embryonic axis induction [ Nat Commun, 2024, 15(1):10028] PubMed: 39562571
Identification of Selective ATP-Competitive CMG Helicase Inhibitors for Cancer Intervention that Disrupt CMG-Replisome Function [ Res Sq, 2023, rs.3.rs-3182731] PubMed: 37609279
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Non-catalytic allostery in α-TAT1 by a phospho-switch drives dynamic microtubule acetylation [ J Cell Biol, 2022, 221-11e202202100] PubMed: 36222836
Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations [ Elife, 2022, 11e78136] PubMed: 36040792
Interleukin-15 enhanced the survival of human γδT cells by regulating the expression of Mcl-1 in neuroblastoma [ Cell Death Discov, 2022, 8(1):139] PubMed: 35351861
Modulation of Primary Cilia by Alvocidib Inhibition of CILK1 [ Int J Mol Sci, 2022, 23(15)8121] PubMed: 35897693
O-GlcNAc transferase maintains metabolic homeostasis in response to CDK9 inhibition [ Glycobiology, 2022, cwac038] PubMed: 35708495

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.