AZD1390 |CAS 2089288-03-7|DC Chemicals

Cas No.:	2089288-03-7
SMILES:	CC(C)N1C2=C(C=NC3=CC(=C(C=C32)C4=CN=C(C=C4)OCCCN5CCCCC5)F)N(C1=O)C
Formula:	C₂₇H₃₂FN₅O₂
M.Wt:	477.57
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:

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. 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. 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.

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