In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml
Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 (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. This compound radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more radiosensitized than wild type. It results in increased genome instability.
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 tumour 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 this compound with radiotherapy, compared to radiotherapy treatment alone. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, this compound dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induces tumour regressions and increased animal survival compared to IR treatment alone. This compound has favourable physical, chemical, PK, and PD properties suitable for clinical applications that require exposures within the central nervous system.
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 this 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).
a lung NCI-H2228 xenograftmodel either implanted into nude mice brains directly (intracranial brain) or injected into the carotid artery [intracarotid artery (ICA)]
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]
RETURN POLICY
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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.
