Ceralasertib (AZD6738)

製品コードS7693 バッチS769303

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

C20H24N6O2S
分子量 412.51 CAS No. 1352226-88-0
Solubility (25°C)* 体外 DMSO 82 mg/mL (198.78 mM)
Ethanol 82 mg/mL warmed with 50ºC water bath (198.78 mM)
Water Insoluble
* <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 Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.
in vitro

In four Kras mutant cell lines: H23, H460, A549, and H358, AZD6738 inhibits ATR kinase activity and impairs cell viability. In ATM-deficient H23 cells, AZD6738 strongly synergizes with NSC 119875 to induce rapid cell death. [1] In p53 or ATM defective cells, AZD6738 treatment results in replication fork stalls and accumulation of unrepaired DNA damage, resulting in cell death by mitotic catastrophe. [2]
in vivo

In nude mice bearing H460 and H23 tumors, AZD6738 (50 mg/kg, p.o.) results in tumor growth inhibition (TGI), and the the combination with NSC 119875 causes rapid regression of ATM-deficient H23 tumors. [1] In nude mice bearing LoVo xenografts, a combination of AZD6738 (50 mg/kg) + IR (2 Gy) avoids toxicity while still maintaining efficacy. [3]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 H23, H460, A549, and H358 cells
濃度 ~30 μM
反応時間 48 h
実験の流れ

Cells are treated in white walled, clear bottom 96-well plates with the indicated doses of AZD6738, NSC 119875, LY-188011, or combination for 48 h. ATP levels are assessed as surrogate measure of viability is assessed using the CellTiter-Glo Luminescent Cell Viability Assay and Safire2 plate reader. Raw data are corrected for background luminescence prior to further analysis. For AZD6738 treatment, log dose response curves are generated in GraphPad Prism 6 by nonlinear regression (log(inhibitor) vs. response with variable slope) of log-transformed (x = log(x)) data normalized to the mean of untreated controls. GI50 values, defined as the dose X at which Y = 50%, were extrapolated from dose response curves.
動物実験 動物モデル Female athymic nude mice bearing H23 or H460 xenografts
投薬量 25 or 50 mg/kg
投与方法 p.o.

カスタマーフィードバック

Data from [Data independently produced by , , Clin Cancer Res, 2018, doi:10.1158/1078-0432.CCR-18-1346]

Data from [Data independently produced by , , J Exp Clin Cancer Res, 2018, 37(1):205]

Data from [Data independently produced by , , Sci Rep, 2017, 7:41950]

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：

Deregulated DNA ADP-ribosylation impairs telomere replication [ Nat Struct Mol Biol, 2024, 10.1038/s41594-024-01279-6] PubMed: 38714889
H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours [ Nat Commun, 2024, 15(1):4430] PubMed: 38789420
Functionally-instructed modifiers of response to ATR inhibition in experimental glioma [ J Exp Clin Cancer Res, 2024, 43(1):77] PubMed: 38475864
Loss of POLE3-POLE4 unleashes replicative gap accumulation upon treatment with PARP inhibitors [ Cell Rep, 2024, 43(5):114205] PubMed: 38753485
ATR inhibition radiosensitizes cells through augmented DNA Damage and G2 cell cycle arrest abrogation [ JCI Insight, 2024, e179599] PubMed: 39235982
KRASG 12C-inhibitor-based combination therapies for pancreatic cancer: insights from drug screening [ Mol Oncol, 2024, 10.1002/1878-0261.13725] PubMed: 39253995
Diffusion of activated ATM explains γH2AX and MDC1 spread beyond the DNA damage site [ iScience, 2024, 27(9):110826] PubMed: 39310780
Ruthenium drug BOLD-100 regulates BRAFMT colorectal cancer cell apoptosis through AhR/ROS/ATR signaling axis modulation [ Mol Cancer Res, 2024, 10.1158/1541-7786.MCR-24-0151] PubMed: 39083088
Afatinib or Bevacizumab in combination with Osimertinib efficiently control tumor development in orthotopic murine models of non-small lung cancer [ PLoS One, 2024, 19(6):e0304914] PubMed: 38935790
ATR inhibition activates cancer cell cGAS/STING-interferon signaling and promotes antitumor immunity in small-cell lung cancer [ Sci Adv, 2024, 10(39):eado4618] PubMed: 39331709

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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