AZD1390

Catalog No.S8680 Batch:S868003

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Technical Data

Formula

C27H32FN5O2
Molecular Weight 477.57 CAS No. 2089288-03-7
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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

Selleck's AZD1390 has been cited by 21 publications

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

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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.