AZD1390 |
| カタログ番号GC19468 |
AZD1390は、強力で選択的なATM阻害剤です。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2089288-03-7
Sample solution is provided at 25 µL, 10mM.
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AZD1390 is a novel and selective ataxia-telangiectasia mutated (ATM) kinase inhibitor, distinguished by AZD1390 high efficiency in crossing the blood-brain barrier[1]. By inhibiting ATM kinase activity, AZD1390 blocks the repair signaling of DNA double-strand breaks, thereby enhancing the sensitivity of tumor cells to DNA damage induced by radiotherapy[2-3]. AZD1390 exhibits favorable oral bioavailability and brain distribution, positioning it as a promising clinical candidate for the treatment of central nervous system malignancies [4].
In vitro, pretreatment of head and neck squamous cell carcinoma (HNSCC) cell lines (such as FaDu and A253) with AZD1390 (10nM) for 1 hour, followed by X-ray (1–4Gy) or proton beam therapy (PBT) irradiation, significantly reduced clonogenic survival and inhibited the growth of 3D tumor spheroids[5]. In TP53-mutant glioblastoma cells (e.g., U251, GBM12, GBM43), pretreatment with AZD1390 (10–30nM) for 1 hour prior to X-ray irradiation (2.5–5Gy) synergistically decreased cell survival, induced apoptosis, abrogated G0–G1 phase arrest, increased G2/M phase retention, and led to persistent chromosomal instability and micronucleus formation [6].
In vivo, intraperitoneal administration of AZD1390 (5mg/kg) at 30 minutes, 24 hours, and 48 hours after reperfusion in a mouse model of middle cerebral artery occlusion (MCAO) significantly reduced cerebral infarct volume and improved neurological deficit scores (mNSS), rotarod latency, forelimb grip strength, and foot-fault test performance[7]. In a patient-derived xenograft (PDX) model of breast cancer central nervous system metastasis, oral administration of AZD1390 (20mg/kg) 1 hour before radiotherapy (2.5 Gy/day × 4 days) markedly suppressed the growth of HER2-positive (CM07, CM14) and triple-negative breast cancer (CM16) xenograft tumors[8].
References:
[1] Pike KG, Hunt TA, Barlaam B, et al. Identification of Novel, Selective Ataxia-Telangiectasia Mutated Kinase Inhibitors with the Ability to Penetrate the Blood-Brain Barrier: The Discovery of AZD1390. J Med Chem. 2024 Feb 22;67(4):3090-3111.
[2] Al-Zoubi RM, Garada K, Al Huneidi R, et al. ATM inhibitors in cancer radiotherapy: Mechanisms, clinical development, and future directions. Eur J Med Chem. 2025 Dec 15;300:118137.
[3] Qian C, Li X, Zhang J, et al. Small Molecular Inhibitors That Target ATM for Drug Discovery: Current Research and Potential Prospective. J Med Chem. 2024 Sep 12;67(17):14742-14767.
[4] Jin MH, Oh DY. ATM in DNA repair in cancer. Pharmacol Ther. 2019 Nov;203:107391.
[5] Fabbrizi MR, Doggett TJ, Hughes JR, et al. Inhibition of key DNA double strand break repair protein kinases enhances radiosensitivity of head and neck cancer cells to X-ray and proton irradiation. Cell Death Discov. 2024 Jun 12;10(1):282.
[6] Chen J, Laverty DJ, Talele S, et al. Aberrant ATM signaling and homology-directed DNA repair as a vulnerability of p53-mutant GBM to AZD1390-mediated radiosensitization. Sci Transl Med. 2024 Feb 14;16(734):eadj5962.
[7] Lan Z, Qu LJ, Liang Y, et al. AZD1390, an ataxia telangiectasia mutated inhibitor, attenuates microglia-mediated neuroinflammation and ischemic brain injury. CNS Neurosci Ther. 2024 Apr;30(4):e14696.
[8] Tew BY, Kalfa AJ, Yang Z, et al. ATM-Inhibitor AZD1390 Is a Radiosensitizer for Breast Cancer CNS Metastasis. Clin Cancer Res. 2023 Nov 1;29(21):4492-4503.
| Cell experiment [1]: | |
Cell lines | FaDu, A253, Detroit 562, UMSCC12, UMSCC74A, and UMSCC6 cells (human head and neck squamous cell carcinoma cell lines) |
Preparation Method | Cells were maintained in Dulbecco's Modified Eagle Medium (DMEM) or Modified Eagle Medium (MEM) supplemented with 10% fetal bovine serum (FBS), 2mM L-glutamine, penicillin-streptomycin, and non-essential amino acids at 37°C, 5% CO₂. Cells were pretreated with the AZD1390 (10nM) for 1 hour prior to irradiation. |
Reaction Conditions | 10nM; 1h pretreatment |
Applications | AZD1390 significantly decreased the clonogenic survival of cell following both X-ray and proton irradiation, with dose enhancement ratios. AZD1390 also reduced the growth of HNSCC cells grown as 3D spheroids, particularly in combination with radiation. |
| Animal experiment [2]: | |
Animal models | Female NOG mice (4- to 6-week-old) with subcutaneous breast cancer patient-derived xenograft (PDX) tumors (CM07, CM14, CM16) |
Preparation Method | Mice were administered AZD1390 (20mg/kg/day) by oral gavage for 4 days, 1 hour prior to each fraction of radiation therapy (2.5Gy/day for 4 days). Tumors were implanted subcutaneously in the flank, and treatment began when the average tumor volume reached 70mm³. |
Dosage form | 20mg/kg/day; oral gavage |
Applications | Pretreatment with AZD1390 followed by radiation therapy significantly inhibited tumor growth in all three PDX models compared to radiation alone. The combination therapy resulted in sustained tumor inhibition and improved animal survival. |
References: | |
| Cas No. | 2089288-03-7 | SDF | |
| Chemical Name | 7-fluoro-1-isopropyl-3-methyl-8-(6-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one | ||
| Canonical SMILES | FC(C=C(N=CC(N1C)=C2N(C(C)C)C1=O)C2=C3)=C3C(C=N4)=CC=C4OCCCN5CCCCC5 | ||
| Formula | C27H32FN5O2 | M.Wt | 477.57 |
| 溶解度 | DMSO : 5 mg/mL (10.47 mM; ultrasonic and warming and heat to 60°C) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0939 mL | 10.4697 mL | 20.9393 mL |
| 5 mM | 418.8 μL | 2.0939 mL | 4.1879 mL |
| 10 mM | 209.4 μL | 1.047 mL | 2.0939 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 34 reference(s) in Google Scholar.)
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