Kinase profiling during drug discovery is a necessary process to confirm inhibitor selectivity and assess off-target activities. However, cost and logistical limitations prevent profiling activities from being performed in-house. We describe the development of an automated and flexible kinase profiling workflow that combines ready-to-use kinase enzymes and substrates in convenient eight-tube strips, a bench-top liquid handling device, ADP-Glo Kinase Assay (Promega, Madison, WI) technology to quantify enzyme activity, and a multimode detection instrument. Automated methods were developed for kinase reactions and quantification reactions to be assembled on a Gilson (Middleton, WI) PIPETMAX, following standardized plate layouts for single- and multidose compound profiling. Pipetting protocols were customized at runtime based on user-provided information, including compound number, increment for compound titrations, and number of kinase families to use. After the automated liquid handling procedures, a GloMax Discover (Promega) microplate reader preloaded with SMART protocols was used for luminescence detection and automatic data analysis. The functionality of the automated workflow was evaluated with several compound-kinase combinations in single-dose or dose-response profiling formats. Known target-specific inhibitions were confirmed. Novel small molecule-kinase interactions, including off-target inhibitions, were identified and confirmed in secondary studies. By adopting this streamlined profiling process, researchers can quickly and efficiently profile compounds of interest on site.

Web traffic is increasingly trending towards mobile devices driving developers to tailor web content to small screens and customize web apps using mobile-only capabilities such as geo-location, accelerometers, offline storage, and camera features. Hybrid apps provide a cross-platform, device independent, means for developers to utilize these features. They work by wrapping web-based code, i.e., HTML5, CSS, and JavaScript, in thin native containers that expose device features. This design pattern encourages re-use of existing code, reduces development time, and leverages existing web development talent that doesn't depend on platform specific languages. Despite these advantages, the newness of hybrid apps raises new security challenges associated with integrating code designed for a web browser with features native to a mobile device. This paper explores these security concerns and defines three forms of attack that can specifically target and exploit hybrid apps connected to web services. Contributions of the paper include a high level process for discovering hybrid app attacks and vulnerabilities, definitions of emerging hybrid attack vectors, and a testbed platform for analyzing vulnerabilities. As an evaluation, hybrid attacks are analyzed in the testbed showing that it provides insight into vulnerabilities and helps assess risk.

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