Molecular Formula | C27H32FN5O2 |
Molar Mass | 477.57 |
Density | 1.224±0.06 g/cm3(Predicted) |
Boling Point | 617.4±55.0 °C(Predicted) |
Solubility | Soluble in DMSO |
pKa | 9.22±0.10(Predicted) |
Storage Condition | 2-8°C |
Use | AZD1390 is an effective, highly selective, orally bioavailable, brain-permeable ATM inhibitor with an IC50 of 0.78 nM to ATM in cells. |
In vitro study | AZD1390 inhibits the activity of DNA damage response dependent on ATM, and combined with radiation treatment can induce cell accumulation in the G2 cycle, causing micronucleus and apoptosis. Treatment with AZD1390 sensitizes glioma and lung cancer cell lines to radiation, and glioma cells carrying p53 mutants are more sensitive to radiation than glioma cells carrying wild-type p53. |
In vivo study | AZD1390 had good oral bioavailability in preclinical studies in various animal models studied (66% in rats and 74% in dogs). In non-human primate PET studies, AZD1390 was able to effectively penetrate the blood-brain barrier. In an orthotopic xenograft brain tumor model, a combination of AZD1390 and radiotherapy for 2 or 4 days resulted in significant tumor regression and improved survival compared to radiotherapy alone. Combination of AZD1390 and ionizing radiation (whole brain or stereotactic radiotherapy) in in vivo, homologous or patient-derived glioma or orthotopic xenograft lung-brain tumor metastasis models, treatment with ionizing radiation alone may result in significant tumor regression and improved animal survival. AZD1390 has good physical, chemical, pharmacokinetic and pharmacodynamic properties, which is suitable for clinical drug development in the central nervous system. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.094 ml | 10.47 ml | 20.939 ml |
5 mM | 0.419 ml | 2.094 ml | 4.188 ml |
10 mM | 0.209 ml | 1.047 ml | 2.094 ml |
5 mM | 0.042 ml | 0.209 ml | 0.419 ml |