AZD1390

製品コードS8680 バッチS868003

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

C27H32FN5O2
分子量 477.57 CAS No. 2089288-03-7
Solubility (25°C)* 体外 Ethanol 24 mg/mL (50.25 mM)
DMSO 16 mg/mL (33.5 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 AZD1390 is a first-in-class orally available and CNS penetrant ATM inhibitor with an IC50 of 0.78 nM in cells and >10,000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kinases.
in vitro AZD1390 blocks ATM-dependent DDR (DNA damage response) pathway activity and combines with radiation to induce G2 cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more radiosensitized than wild type. AZD1390 results in increased genome instability[2].
in vivo AZD1390 displays excellent oral bioavailability in preclinical species (66% in rat and 74% in dog). It can efficiently cross the BBB in non-human primate PET studies. Profound tumor regressions and increased animal survival (>50 days) have been observed in orthotopic xenograft models of brain cancer following just 2 or 4 days combination treatment of AZD1390 with radiotherapy, compared to radiotherapy treatment alone[1]. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induces tumor regressions and increased animal survival compared to IR treatment alone. AZD1390 has favorable physical, chemical, PK, and PD properties suitable for clinical applications that require exposures within the central nervous system[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 NCI-H2228 cells
濃度 0-1250 nM
反応時間 1 h
実験の流れ

Cells (3000 per well) are seeded in a 384-well format in RPMI with 10% fetal bovine serum.After 24 hours, plates are Echo-dosed with a semi-log dose dilution of each compound from a top concentration of 1250 nM. One hour after compound dosing, plates are irradiated with 0, 2.5, or 4 Gy. At 1, 6, 24, and 48 hours after irradiation, plates are fixed by adding a 1:1 volume of 8% PFA directly to the medium to give a final concentration of 4% PFA and incubated for 30 min at room temperature before washing three times with phosphate-buffered saline solution (PBSA).
動物実験 動物モデル a lung NCI-H2228 xenograftmodel either implanted into nude mice brains directly (intracranial brain) or injected into the carotid artery [intracarotid artery (ICA)]
投薬量 5, 15 and 20 mg/kg
投与方法 by oral gavage

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：

Regulation of transcription patterns, poly(ADP-ribose), and RNA-DNA hybrids by the ATM protein kinase [ Cell Rep, 2024, 43(3):113896] PubMed: 38442018
Galectin-9 blockade synergizes with ATM inhibition to induce potent anti-tumor immunity [ Int J Biol Sci, 2023, 19(3):981-993] PubMed: 36778120
Galectin-9 blockade synergizes with ATM inhibition to induce potent anti-tumor immunity [ Int J Biol Sci, 2023, 19(3):981-993] PubMed: 36778120
A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis [ Cancer Chemother Pharmacol, 2023, 92(1):57-69] PubMed: 37272932
Regulation of transcription patterns, poly-ADP-ribose, and RNA-DNA hybrids by the ATM protein kinase [ bioRxiv, 2023, 2023.12.06.570417] PubMed: 38106035
MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [ Cancer Cell, 2022, S1535-6108(21)00662-0] PubMed: 35051357
Small-molecule targeted therapies induce dependence on DNA double-strand break repair in residual tumor cells [ Sci Transl Med, 2022, 14(638):eabc7480] PubMed: 35353542
Persistent DNA damage associated with ATM kinase deficiency promotes microglial dysfunction [ Nucleic Acids Res, 2022, 50(5):2700-2718] PubMed: 35212385
ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization [ Cell Rep, 2022, 38(2):110216] PubMed: 35021084
Hedgehog interacting protein activates sodium-glucose cotransporter 2 expression and promotes renal tubular epithelial cell senescence in a mouse model of type 1 diabetes [ Diabetologia, 2022, 10.1007/s00125-022-05810-6] PubMed: 36260124

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。