AZD1390

Catalog No.S8680 Batch:S868002

Technical Data

Formula

C₂₇H₃₂FN₅O₂

Molecular Weight

477.57

CAS No.

2089288-03-7

Solubility (25°C)*

In vitro

Ethanol

95 mg/mL (198.92 mM)

DMSO

14 mg/mL (29.31 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

10%DMSO 1 40%PEG300 2 5%TWEEN80 3 45%ddH2O

1.5mg/ml

Taking the 1 mL working solution as an example, add 100 μL of 15 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 450 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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

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].

Protocol (from reference)

Cell Assay:^{^[2]}	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).
Animal Study:^{^[2]}	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

Cell Assay:^{^[2]}

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).

Animal Study:^{^[2]}

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

References

Selleck's AZD1390 has been cited by 25 publications

Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers [ Nature, 2024, 629(8011):443-449]	PubMed: 38658754
Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers [ Nature, 2024, 629(8011):443-449]	PubMed: 38658754
Regulation of transcription patterns, poly(ADP-ribose), and RNA-DNA hybrids by the ATM protein kinase [ Cell Rep, 2024, 43(3):113896]	PubMed: 38442018
Replicative senescence is ATM driven, reversible, and accelerated by hyperactivation of ATM at normoxia [ bioRxiv, 2024, 2024.06.24.600514]	PubMed: 38979390
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
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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.