Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors

Disruption of PH–kinase domain interactions leads to oncogenic activation of AKT in human cancers

“…Given that some AKT1 somatic mutants have impaired PH-KD contacts, we predicted that allosteric inhibitors are likely to be less efficacious in inhibiting their activity. We tested this prediction by assaying the activity of two ATP-competitive inhibitors [GNE-692 (41) and GSK690693 (42)] and two allosteric inhibitors [Inhibitor VIII (43) and GNE-929 ( Fig. S7)] on recombinant fulllength WT and mutant AKT1 enzymes.…”

Drug discovery approaches targeting the PI3K/Akt pathway in cancer

“…It is notable that allosteric inhibitors of Akt containing the 2,3-diphenylquinoxaline or 5,6-diphenyl-pyrazin-2(1H)-one scaffolds have been described Lindsley et al, 2005;Zhao et al, 2005). Here, a high throughput homogenous time-resolved fluorescence kinase assay was used to screen around 270 000 compounds for their ability to inhibit Akt enzymatic activity.…”

Montmorillonite K-10: An efficient and reusable catalyst for the synthesis of quinoxaline derivatives in water

“…Clays function as efficient catalysts for various organic transformations due to their Brønsted and Lewis acidities in both their natural and ion-exchanged forms [4]. Due to strong catalytic activity as Brønsted acid, Mont K-10 clay has been used extensively as a catalyst in: DielsAlder reaction [3a] Quinoxalines are very important compounds due to their wide spectrum of biological activities behaving as anticancer [5], antiviral [6], antibacterial [7], and activity as kinase inhibitors [8]. In addition to medicinal applications, quinoxaline derivatives have been found applications as dyes [9] and building blocks in the synthesis of organic semiconductors [10].…”