CHIR-124

製品コードS2683 バッチS268302

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H22ClN5O
分子量 419.91 CAS No. 405168-58-3
Solubility (25°C)* 体外 DMSO 7 mg/mL (16.67 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.
* <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 CHIR-124は、cell-freeアッセイにおいて0.3 nMのIC50を示す新規かつ強力なChk1阻害剤です。Chk2に対して2,000倍の選択性を示し、CDK2/4およびCdc2に対しては500～5,000倍低い活性を示します。
in vitro

CHIR-124 is a quinolone-based small molecule that is structurally unrelated to other known inhibitors of Chk1. This compound interacts synergistically with topoisomerase poisons (e.g., Camptothecin or SN-38) in causing growth inhibition in a variety of cancer cell lines, including breast carcinoma (MDA-MB-231 and MDA-MB-435) and colon carcinoma (SW-620 and Colo205), all of which contains the mutant p53 gene. It abrogates the SN-38-induced S and G2-M checkpoints and potentiates apoptosis in MDA-MD-435 breast cancer cells. The abrogation of the G2-Mcheckpoint and induction of apoptosis by this chemical are enhanced by the loss of p53. This compound also potently targets other kinases such as PDGFR and Flt3 with IC50 of 6.6 nM and 5.8 nM, respectively.

in vivo

CHIR-124 potentiates the growth inhibitory effects by abrogating the G2-M checkpoint and increasing tumor apoptosis in an orthotopic breast cancer xenograft model.

プロトコル(参考用のみ)

キナーゼアッセイ Chk1 Assay
For the Chk1 assay, the kinase domain is expressed in Sf9 insect cells, and a biotinylated cdc25c peptide containing the consensus Chk1/Chk2 phosphorylation site (*)(biotin-[AHX]SGSGS*GLYRSPSMP-ENLNRPR[CONH2]) is used as the substrate. A dilution series of CHIR-124 is mixed with a kinasereaction buffer containing a final concentration of 30 mM Tris-HCl(pH 7.5), 10 mM MgCl2, 2 mM DTT, 4 mM EDTA, 25 mMβ-glycerophosphate, 5 mM MnCl2, 0.01% bovine serum albumin, 1.35 nM CHK1 kinase domain, 0.5 μM peptide substrate, and 1 AM unlabeled ATP, plus 5 nM 33Pγ-labeled ATP (specific activity = 2,000 Ci/mmol). Reactions and detection of the phosphate transfer are carried out by a radioactive method. Reactions are incubated at room temperature for 1 to 4 hours and the phosphorylated peptide captured on streptavidin-coated microtiter plates containing stop reaction buffer (25 mM EDTA [ethylenediaminetetraacetic acid], 50 mMHEPES, pH 7.5). Phosphorylated peptide is measured with the DELFIA TRF system using a Europium-labeled anti-phosphotyrosine antibody PT66. The concentration of this compound for IC50 is calculated using nonlinear regression with XL-Fit data analysis software.
細胞アッセイ 細胞株 MDA-MB-231, MDA-MB-435, SW-620, and COLO 205 cells
濃度 0-2350 nM, dependent on cell types
反応時間 48 hours
実験の流れ

MDA-MB-231, MDA-MB-435, SW-620, and COLO 205 cells in log-phase are plated into 96-well microplates. CHIR-124 is serially diluted in the presence of six different concentrations of Camptothecin or 0 nM camptothecin. Camptothecin is also serially diluted in the absence of this compound. This chemical is added to cells in 96-well dishes and incubated at 37 °C for 48 hours. Each treatment condition is done in triplicate. Cell proliferation is monitored by the 3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), inner salt assay. MTS inner salt is added to the microplates, which are incubated for another 3 hours, and absorbance at 490 nm is read on a plate reader. The concentrations of each drug in the combinations required to produce 50% inhibition are plotted to generate the isoboles. Isobologram analysis of drug interaction is based the equation of Loewe additivity (1= D A /IC50, A + DB/IC50, B), where IC50, A and IC50, B are the concentrations of drugs to result in 50% inhibition for each drug alone, and DA and DB are concentrations of each drug in the combination that yield 50% overall inhibition. A diagonal line indicating Loewe additivity is included in each graph. Data points that fall below the line indicate synergy, whereas those that fall above the line will indicate antagonism
動物実験 動物モデル MDA-MB-435 cells are implanted in the mammary fat pad of 8- to 10-week-old female immunodeficient mice.
投薬量 10 mg/kg or 20 mg/kg
投与方法 CHIR-124 is given orally four times daily × 6 on days 2 to 7 in captisol.

参考

  • https://pubmed.ncbi.nlm.nih.gov/17255282/
  • https://pubmed.ncbi.nlm.nih.gov/20068082/

カスタマーフィードバック

Data from [Oncotarget, 2014, 5(3), 667-78]

Data from [Data independently produced by , , J Pathol, 2015, 236: 348-359]

Data from [Data independently produced by , , J Virol, 2016, 90(20):9433-45]

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：

A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
The mitotic ATR-Chk1 pathway promotes CDK1 activity for faithful chromosome segregation [ Cell Rep, 2025, 44(8):116019] PubMed: 40705605
Enhancing transcription-replication conflict targets ecDNA-positive cancers [ Nature, 2024, 635(8037):210-218] PubMed: 39506153
The MYCN oncoprotein is an RNA-binding accessory factor of the nuclear exosome targeting complex [ Mol Cell, 2024, S1097-2765(24)00285-5] PubMed: 38703770
Replicative senescence is ATM driven, reversible, and accelerated by hyperactivation of ATM at normoxia [ bioRxiv, 2024, 2024.06.24.600514] PubMed: 38979390
p53-independent tumor suppression by cell-cycle arrest via CREB/ATF transcription factor OASIS [ Cell Rep, 2023, S2211-1247(23)00490-4] PubMed: 37178686
The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway [ NPJ Regen Med, 2023, 8(1):20] PubMed: 37024481
The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway [ npj Regenerative Medicine, 2023, 20-2023)] PubMed: None
Alternative Lengthening of Telomeres in Pediatric High-Grade Glioma and Therapeutic Implications [ Cancers (Basel), 2023, 15(12)3070] PubMed: 37370681
The Autonomous Parvovirus Minute Virus of Mice Localizes to Cellular Sites of DNA Damage Using ATR Signaling [ Viruses, 2023, 15(6)1243] PubMed: 37376543

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。

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