A Novel, Potent, Small Molecule AKT Inhibitor Exhibits Efficacy against Lung Cancer Cells In Vitro / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
;
: 913-920, 2015.
Article
Dans Anglais
| WPRIM
| ID: wpr-90547
ABSTRACT
PURPOSE:
Anomalies of Akt regulation, including overexpression in lung cancer, impart resistance to conventional chemotherapy and radiation, thereby implicating this kinase as a therapeutic intervention point. A novel scaffold of Akt inhibitors was developed through virtual screening of chemical databases available at Birla Institute of Technology and Science, Pilani, Hyderabad, based on docking studies using Maestro. A benzothienopyrimidine derivative (BIA-6) was identified as a potential lead molecule that inhibited Akt1 enzyme activity with an IC50 of 256 nM. MATERIALS ANDMETHODS:
BIA-6 was tested for in vitro Akt1 inhibition using a fluorescence resonance energy transfer kit. Anti-proliferative activity was tested in NCI-H460, A549, NCI-H1975, and NCI-H2170 cell lines. The effect of the compound on p-Akt (S473) was estimated.RESULTS:
BIA-6 allosterically caused a dose dependent reduction of growth of cell lines with a half maximal growth inhibition (GI50) range of 0.49 muM to 6.6 muM. Cell cycle analysis indicated that BIA-6 caused a G1 phase arrest at < 100 nM but led to apoptosis at higher doses. BIA-6 also exhibited synergism with standard chemotherapeutic agents.CONCLUSION:
BIA-6 is a novel, allosteric Akt inhibitor with potent anti-cancer activity in lung cancer cell lines, that effectively blocks the phosphoinositide-3 kinase/Akt pathway with a high margin selectivity towards normal cells.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Phosphotransferases
/
Cycle cellulaire
/
Lignée cellulaire
/
Dépistage de masse
/
Phase G1
/
Apoptose
/
Carcinome pulmonaire non à petites cellules
/
Concentration inhibitrice 50
/
Transfert d'énergie par résonance de fluorescence
/
Synergie des médicaments
Type d'étude:
Étude de dépistage
langue:
Anglais
Texte intégral:
Cancer Research and Treatment
Année:
2015
Type:
Article
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