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SML2551

Sigma-Aldrich

AZ32

≥98% (HPLC)

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Synonym(s):
N-Methyl-4-(6-phenylimidazo[1,2-a]pyrazin-3-yl)benzamide
Empirical Formula (Hill Notation):
C20H16N4O
CAS Number:
2288709-96-4
Molecular Weight:
328.37
MDL number:
MFCD31715431

Assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

2-8°C

Biochem/physiol Actions

AZ32 is an orally active, potent and selective ataxia telangiectasia mutated (ATM) kinase inhibitor (IC50 <6.2 nM; DNA-PK & PI3Ka IC50 =4.6 μM, hERG IC50 = 17.6 μM) with good aqueous solubility (24 μM) and blood-brain barrier (BBB) permeability in mice (free brain/plasma ratio = 0.26; 200 mg/kg p.o.). AZ32 exhibits radiosensitizing efficacy in human & murine glioma cultures by blocking radiation-induced DNA damage response (ATM pS1981 IC50 = 310 nM; 100% blockage of KAP1 pS824 & p53 pS15 at 300 nM; T98G cells). AZ32 (200 mg/kg/day p.o.) improves whole-head irradiation treatment survival rate among mice with brain GL261 tumors or NCI-H2228 NSCLC metastases in vivo.

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Regulatory Information

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Jeremy Karlin et al.
Molecular cancer therapeutics, 17(8), 1637-1647 (2018-05-18)
Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited central nervous system (CNS) bioavailability;

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