AZD1390

AZD1390 is a first-in-class orally available and CNS penetrantATMinhibitor 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.TargetsATM (Cell-based assay) 0.78 nMIn vitroAZD1390 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 vivoAZD1390 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.Cell Research(from reference)Cell lines：NCI-H2228 cells Concentrations：0-1250 nM Incubation Time：1 h

ATM Selective Inhibitors | Activators

Specifications & Purity: AZD1390 is a first-in-class orally available and CNS penetrantATMinhibitor 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.TargetsATM (Cell-based assay) 0.78 nMIn vitroAZD1390 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 vivoAZD1390 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.Cell Research(from reference)Cell lines：NCI-H2228 cells Concentrations：0-1250 nM Incubation Time：1 h

Grade: Moligand™

Molecular Formula: C27H32FN5O2

Molecular Weight: 477.57

PubChem CID: 126689157

Isomeric SMILES: CC(C)N1C2=C(C=NC3=CC(=C(C=C32)C4=CN=C(C=C4)OCCCN5CCCCC5)F)N(C1=O)C

Storage Temperature: Store at -20°C

Shipped in: Ice chest + Ice pads

UPC:

51294515

Weight:

1.06 Ounces

HazmatClass:

Yes

Quantity:

1

Unit of Measurement:

EA

WeightUOM:

LB

MPN:

A414112-1mg

Country of Origin:

China

CAS:

2089288-03-7

Product Size:

1mg

Harmonized Tariff Code:

2931.90.90