1-(6,7-dimethoxyquinazolin-4-yl)-3-(pyridin-2-yl)-1H-1,2,4-triazol-5-amine

• ChemBase ID: 73109
• Molecular Formular: C17H15N7O2
• Molecular Mass: 349.3467
• Monoisotopic Mass: 349.12872276
• SMILES: c1cccnc1c1nn(c(n1)N)c1c2c(ncn1)cc(c(c2)OC)OC
• Canonical SMILES: COc1cc2c(cc1OC)ncnc2n1nc(nc1N)c1ccccn1
• InChI: InChI=1S/C17H15N7O2/c1-25-13-7-10-12(8-14(13)26-2)20-9-21-16(10)24-17(18)22-15(23-24)11-5-3-4-6-19-11/h3-9H,1-2H3,(H2,18,22,23)
• InChIKey: ILBRKJBKDGCSCB-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-(6,7-dimethoxyquinazolin-4-yl)-3-(pyridin-2-yl)-1H-1,2,4-triazol-5-amine
• IUPAC Traditional name: 2-(6,7-dimethoxyquinazolin-4-yl)-5-(pyridin-2-yl)-1,2,4-triazol-3-amine
• Synonyms: CP466722; CP-466722

Database IDs

• CAS Number: 1080622-86-1
• PubChem SID: 162038029
• PubChem CID: 44551660

CALCULATED PROPERTIES

• H Acceptors: 8
• H Donor: 1
• LogD (pH = 5.5): 2.3357136
• LogD (pH = 7.4): 2.3488157
• Log P: 2.3489854
• Molar Refractivity: 106.6321 cm^3
• Polarizability: 37.12973 Å^3
• Polar Surface Area: 113.86 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: ATM

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2245

Research Area

• Description: Cancer

Biological Activity

• Description: CP-466722 is an potent and reversible ATM inhibitor.
• Targets: ATM
• In Vitro: In vitro, CP-466722 is identified as a potential inhibitor to decrease the activity of purified ATM kinase to phosphorylate GST-p53(1–101) substrate. In addition, CP-466722 also shows the inhibitory activities against abl and src kinases. ^[1] In HeLa cells, CP-466722 at doses of 6μM, results in the inhibition in ATM-dependent phosphorylation by reversibly inhibiting ionizing radiation (IR)-induced ATM kinase activity. Besides, ATM-dependent p53 induction is also inhibited by CP-466722 in MCF-7 human breast cancer cells and primary and immortalized diploid human fibroblasts. ^[1] In response to IR, CP-466722 increased proportion of cells with G2/M DNA content and reduces proportion of cells with G1-phase DNA content in HeLa cells. ^[1] Transient exposure to CP-466722 for a period of 4 hours sensitizes HeLa cells to IR without affecting cell plating nor cell viability. ^[1]

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: HeLa and A-T
• Concentrations: 0-6 μM
• Incubation Time: 4 hours
• Methods: HeLa or A-T (GM02052 expressing hTERT) cells are plated in triplicate and incubated for 24 hours. Cells are pre-treated: DMSO, CP466722 or KU55933 prior to IR (0-10Gy). Cells are incubated for 4 hours following IR before media is removed, cells washed (PBS), trypsinsed, counted and re-plated (2000 cells/plate, 10 cm plates) in the absence of drug and incubated for 10 days. Prior to colony counting, cells are washed (PBS), stained (PBS, 0.0037%v/v-formaldehyde, 0.1%w/v-crystal violet), rinsed (dH₂O) and dried. Defined populations (>50 cells) are counted as one surviving colony, data are calculated as percentage surviving colonies relative to control plates +/? SE.

References

• References: [1] Rainey MD, et al. Cancer Res, 2008, 68(18), 7466-7474.

REFERENCES

• Rainey MD, et al. Cancer Res, 2008, 68(18), 7466-7474.