Home PI3K/Akt/mTOR ATM/ATR inhibitor AZD1390 For research use only.

AZD1390

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.

AZD1390 Chemical Structure

AZD1390 Chemical Structure

CAS No. 2089288-03-7

Purity & Quality Control

AZD1390 Related Products

Signaling Pathway

ATM/ATR Signaling Pathways

ATM/ATR Signaling Pathway

Biological Activity

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.
Targets
ATM [1]
(Cell-based assay)
0.78 nM
In vitro
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].
Cell Research 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).
Experimental Result Images Methods Biomarkers Images PMID
Western blot pChk2 pATM (S1981) / ATM / pKAP1(S824) / KAP1 / pCDK1 29938225
In Vivo
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].
Animal Research 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
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05182905 Recruiting
Glioblastoma|Glioma|Glioblastoma Multiforme|Glioma Malignant
Nader Sanai|Barrow Neurological Institute|Ivy Brain Tumor Center|AstraZeneca|St. Joseph''s Hospital and Medical Center Phoenix
 March 9 2022 Early Phase 1
NCT03423628 Recruiting
Recurrent Glioblastoma Multiforme|Primary Glioblastoma Multiforme|Brain Neoplasms Malignant|Leptomeningeal Disease (LMD)
AstraZeneca
 April 2 2018 Phase 1
NCT03215381 Completed
Healthy Volunteer Male Subjects
AstraZeneca|Karolinska Institutet Quintiles IMS
 October 10 2017 Phase 1

Chemical Information & Solubility

Molecular Weight 477.57 Formula

C27H32FN5O2
CAS No. 2089288-03-7 SDF --
Smiles CC(C)N1C2=C(C=NC3=CC(=C(C=C32)C4=CN=C(C=C4)OCCCN5CCCCC5)F)N(C1=O)C
Storage (From the date of receipt)

In vitro
Batch:

Ethanol : 95 mg/mL

DMSO : 14 mg/mL ( (29.31 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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