AT7519

製品コードS1524 バッチS152402

印刷

化学情報

Synonyms

AT7519M

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₆H₁₇Cl₂N₅O₂

分子量

382.24

CAS No.

844442-38-2

Solubility (25°C)*

体外

DMSO

25 mg/mL (65.4 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

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.
Clear solution	2%DMSO 1 30%PEG300 2 2%Tween80 3 66%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.000mg/ml (2.62mM)	Taking the 1 mL working solution as an example, add 20 μL of 50 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	AT7519 は、CDK1、2、4、6、9 に対するマルチCDK阻害剤であり、IC50 は 10-210 nM です。CDK3 に対しては効力が弱く、CDK7 に対してはほとんど活性がありません。AT7519 はGSK3β のリン酸化も減少させます。AT7519 はapoptosis を誘導します。フェーズ2。
in vitro	AT7519 is an ATP competitive CDK inhibitor with a K_i 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. 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.
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. 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.

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro Kinase Assays
キナーゼアッセイ	[API调用失败: invalid chat.event: ping, {'event': 'ping', 'data': '{"timestamp_ms":"1763712465092"}'}]
細胞アッセイ	細胞株	MM.1S, MM.1R, RPMI8226, U266, RPMI8266, RPMI-Dox40, OPM1 cells, primary MM cells and PBMNCs
	濃度	Dissolved in DMSO at a concentration of 10 mM, final concentrations 0.25-4 μM
	反応時間	24 or 48 hours
	実験の流れ	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).
動物実験	動物モデル	Male SCID mice inoculated subcutaneously with MM.1S cells
	投薬量	15 mg/kg/day
	投与方法	Dosed i.p.

参考

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

カスタマーフィードバック

: Data from [Data independently produced by AIDS, 2014, 28(15), 2213-22]

: Data from [Data independently produced by PLoS One, 2011, 6(9), e25683]

: , , Dr. Srinivas Narasipura of Rush University Medical Center

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。