The serine/threonine Akt kinase signaling pathway plays an essential role not only in tumorigenesis but also in the potential response to anticancer therapeutic agents. Therefore, aiming to identify potent and selecti...The serine/threonine Akt kinase signaling pathway plays an essential role not only in tumorigenesis but also in the potential response to anticancer therapeutic agents. Therefore, aiming to identify potent and selective Akt inhibitors, a novel series of benzimidazole derivatives w<span style="font-family:Verdana;">ere<span style="font-family:Verdana;"> designed and docked within the crystal structure of Akt1 kinase. In order to predict their selectivity, the hit compounds were docked against the protein kinase A (PKA), which is the closely related AGC family kinase protein. Moreover, <span style="white-space:nowrap;font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">in<span style="font-family:Verdana;">-<span style="font-family:Verdana;">silico<span style="white-space:nowrap;font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> ADMET-related descriptors were estimated to predict the pharmacokinetic properties for the selected compounds. Among the designed molecules, four compounds were found to have the best binding affinity and good selectivity to Akt1 kinase, furthermore, those compounds had acceptable ADMET properties and <span style="font-family:Verdana;">were <span style="font-family:Verdana;">predicted to be non-mutagenic, which could account them as promising Akt1 inhibitory agents for further investigations.展开更多
文摘The serine/threonine Akt kinase signaling pathway plays an essential role not only in tumorigenesis but also in the potential response to anticancer therapeutic agents. Therefore, aiming to identify potent and selective Akt inhibitors, a novel series of benzimidazole derivatives w<span style="font-family:Verdana;">ere<span style="font-family:Verdana;"> designed and docked within the crystal structure of Akt1 kinase. In order to predict their selectivity, the hit compounds were docked against the protein kinase A (PKA), which is the closely related AGC family kinase protein. Moreover, <span style="white-space:nowrap;font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">in<span style="font-family:Verdana;">-<span style="font-family:Verdana;">silico<span style="white-space:nowrap;font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> ADMET-related descriptors were estimated to predict the pharmacokinetic properties for the selected compounds. Among the designed molecules, four compounds were found to have the best binding affinity and good selectivity to Akt1 kinase, furthermore, those compounds had acceptable ADMET properties and <span style="font-family:Verdana;">were <span style="font-family:Verdana;">predicted to be non-mutagenic, which could account them as promising Akt1 inhibitory agents for further investigations.
