For research use only.

Catalog No.S8680

6 publications

AZD1390 Chemical Structure

CAS No. 2089288-03-7

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.

Selleck's AZD1390 has been cited by 6 publications

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Description 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.
ATM [1]
(Cell-based assay)
0.78 nM
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].

Methods Test Index PMID
Western blot
pATM (S1981) / ATM / pKAP1(S824) / KAP1 / pCDK1 ; 

PubMed: 29938225     

AZD1390 cellular target engagement using phospho-Ser1981 ATM and downstream pathway modulation demonstrating dose-dependent (0 to 300 nM) target engagement (pATM) in LN18 GBM cells at 4-hour time points. Effect of AZD6738 (ATR inhibitor), AZD1775 (Wee1 inhibitor), and AZD2281 (PARP inhibitor, olaparib/Lynparza) selective clinical inhibitors.


PubMed: 29938225     

(F) ATM pathway modulation by AZD1390 in three GBM cell lines indicated. Reduction in IR-induced cell cycle checkpoint (pChk2) by AZD1390 after 6 hours of incubation in the drug, confirmed in three p53 mutant GBM cell lines indicated.

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].


Cell Research:


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  • Cell lines: NCI-H2228 cells
  • Concentrations: 0-1250 nM
  • Incubation Time: 1 h
  • Method:

    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).

    (Only for Reference)
Animal Research:


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  • Animal Models: a lung NCI-H2228 xenograftmodel either implanted into nude mice brains directly (intracranial brain) or injected into the carotid artery [intracarotid artery (ICA)]
  • Dosages: 5, 15 and 20 mg/kg
  • Administration: by oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro Ethanol 95 mg/mL (198.92 mM)
DMSO 14 mg/mL (29.31 mM)
Water 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.

Chemical Information

Molecular Weight 477.57


CAS No. 2089288-03-7
Storage powder
in solvent
Synonyms N/A
Smiles CC(C)N1C2=C(C=NC3=CC(=C(C=C32)C4=CN=C(C=C4)OCCCN5CCCCC5)F)N(C1=O)C

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03423628 Recruiting Radiation: Radiation Therapy|Drug: AZD1390 Recurrent Glioblastoma Multiforme|Primary Glioblastoma Multiforme|Brain Neoplasms Malignant|Leptomeningeal Disease (LMD) AstraZeneca April 2 2018 Phase 1
NCT03215381 Completed Drug: [11C]AZD1390 Healthy Volunteer Male Subjects AstraZeneca|Karolinska Institutet Quintiles IMS October 10 2017 Phase 1

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ATM/ATR Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID