AZ32 (C09-0735-621)

InformationAZ32 is a specific inhibitor of theATM kinasethat possesses good BBB penetration in mouse with an IC50 value of <0.0062 μM for ATM enzyme. It shows adequate selectivity over ATR and also has high cell permeability.TargetsATM (Cell-free assay) <0.0062 μMIn vitroAZ32 blocks the DNA damage response (DDR) and radiosensitized GBM cells in vitro. AZ32 shows moderate potency against ATM in cell (IC50 = 0.31 μM) and adequate selectivity over ATR, while also having high cell permeability.In vivoAZ32, with enhanced blood-brain barrier (BBB) penetration, was highly efficient in vivo as radiosensitizer in syngeneic and human, orthotopic mouse glioma model compared with AZ31. AZ32 is the first ATMi with oral bioavailability shown to radiosensitize glioma and improve survival in orthotopic mouse models. Following a single oral dose of AZ32 (200 mg/kg) in mice, the free brain concentrations of AZ32 was in excess of the cellular IC50 for approximately 22 hr. AZ32 has enhanced BBB penetration at 8.7-fold and improved brain coverage over AZ31 but with reduced ATM selectivity.Cell Research(from reference)Cell lines：U1242 cells Concentrations：3 μM Incubation Time：48 h. Specifications and Purity: 99%. Molecular Formula: C20H16N4O. Molecular Weight: 328.37. PubChem CID: 134814488. Isomeric SMILES: CNC(=O)C1=CC=C(C=C1)C2=CN=C3N2C=C(N=C3)C4=CC=CC=C4. Related Document: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/A414140-SCI_65cadfd0ab773ebb952ab6fe33e93a68.pdf