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Purity: ≥98%
AZD1390 (AZD-1390) is a novel, potent, selective, first-in-class orally bioavailable and CNS penetrant inhibitor of Ataxia-telangiectasia mutated (ATM) kinase with potential anticancer activity. In cell assays, it inhibits ATM with an IC50 of 0.78 nM. It exhibits excellent selectivity across a wide range of kinases and is >10,000 fold more selective than the closely related PIKK family of enzymes. Treating intracranial malignancies is appropriate for AZD1390 because it can cross the blood-brain barrier (BBB). Both lung cancer and glioma cell lines are radiosensitized by AZD1390; p53 mutant glioma cells are typically more radiosensitized than wild type. As a radiosensitizer for tumors of the central nervous system, AZD1390 is currently in the early stages of clinical research.
Targets |
ATM ( IC50 = 0.78 nM )
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ln Vitro |
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ln Vivo |
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Cell Assay |
In an RPMI format, 3000 cells per well are seeded using 10% fetal bovine serum in a 384-well format.Plates are Echo-dosed with a semi-log dose dilution of each compound after a 24-hour period, starting at a top concentration of 1250 nM. After compound dosing, plates are exposed to 0, 2.5, or 4 Gy of radiation for one hour. After the plates are fixed at 1, 6, 24, and 48 hours after the radiation, they are incubated for 30 minutes at room temperature and then three times with phosphate-buffered saline solution (PBSA). This is done by directly adding a 1:1 volume of 8% PFA to the medium, resulting in a final concentration of 4% PFA.
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Animal Protocol |
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References |
Molecular Formula |
C27H32FN5O2
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Molecular Weight |
477.57
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Exact Mass |
477.25
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Elemental Analysis |
C, 67.90; H, 6.75; F, 3.98; N, 14.66; O, 6.70
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CAS # |
2089288-03-7
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Appearance |
Solid powder
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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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InChi Key |
VQSZIPCGAGVRRP-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C27H32FN5O2/c1-18(2)33-26-21-14-20(22(28)15-23(21)29-17-24(26)31(3)27(33)34)19-8-9-25(30-16-19)35-13-7-12-32-10-5-4-6-11-32/h8-9,14-18H,4-7,10-13H2,1-3H3
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Chemical Name |
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0939 mL | 10.4697 mL | 20.9393 mL | |
5 mM | 0.4188 mL | 2.0939 mL | 4.1879 mL | |
10 mM | 0.2094 mL | 1.0470 mL | 2.0939 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT04550104 | Recruiting | Drug: AZD1390 Drug: TBD Compound 1 |
Non Small Cell Lung Cancer | University of Leeds | March 17, 2021 | Phase 1 |
NCT05116254 | Recruiting | Combination Product: AZD1390 + radiotherapy |
Soft Tissue Sarcoma Adult | The Netherlands Cancer Institute | July 18, 2022 | Phase 1 |
NCT05678010 | Recruiting | Radiation: Stereotactic Body Radiotherapy Drug: AZD1390 |
Solid Tumor Solid Carcinoma |
Memorial Sloan Kettering Cancer Center |
May 17, 2023 | Phase 1 |
NCT03423628 | Recruiting | Radiation: Radiation Therapy Drug: AZD1390 |
Brain Neoplasms, Malignant Leptomeningeal Disease (LMD) |
AstraZeneca | April 2, 2018 | Phase 1 |
NCT05182905 | Recruiting | Drug: AZD1390 | Glioblastoma Glioma |
Nader Sanai | March 9, 2022 | Early Phase 1 |
The structure and brain-penetrating properties of AZD1390.Science Advances. 2018, 4(6): eaat1719. th> |
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Target engagement and cellular mechanism of action of AZD1390.Science Advances. 2018, 4(6): eaat1719. td> |
In vivo activity of AZD1390 in lung-brain metastatic models.Science Advances. 2018, 4(6): eaat1719. td> |
Survival of a syngeneic mouse model of GBM treated with AZD1390.Science Advances. 2018, 4(6): eaat1719. th> |
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In vivo subcutaneous efficacy studies using PDX models.Science Advances. 2018, 4(6): eaat1719. td> |
harmacokinetics and pharmacodynamicsof AZD1390.Science Advances. 2018, 4(6): eaat1719. td> |