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Quantitative chemoproteomics has recently emerged as an experimental approach to determine protein interaction profiles of small molecules in a given cell line or tissue. In contrast to standard biochemical and biophysical kinase assays, application of this method to kinase inhi ...

Protein phosphorylation represents the most dominant and evolutionary conserved posttranslational modification for information transfer in cells and organisms. The human genome encodes 500 protein kinases, and thousands of phosphorylation sites are present in mammali ...

Receptor tyrosine kinases (RTK) are important targets in drug discovery processes. Studying the phosphorylation pattern of RTKs enables the determination of their activation and inactivation states. Multiplex bead-based sandwich immunoassays are powerful tools for measu ...

Phosphoproteomic networks mediated by protein kinases are the key drivers of proliferative and survival signals underlying human cancers, and as such a number of kinases have been the subject of intensive drug discovery efforts. A key question that must be answered during clinical devel ...

Protein and lipid kinases fulfill essential roles in many signaling pathways that regulate normal cell functions. Deregulation of these kinase activities lead to a variety of pathologies ranging from cancer to inflammatory diseases, diabetes, infectious diseases, cardiovasc ...

Clinical tools to accurately describe, evaluate, and predict an individual’s response to cancer therapy are a field-wide priority; in many advanced cancers, only 10–20% of individuals will have a clinical benefit from therapy, yet we treat the entire population. Furthermore, many therap ...

The inflammatory response requires complex and coordinated cooperation of different signaling pathways and cell types. Therefore, more than 40 different protein or lipid kinases can be regarded as potential small-molecule inhibitor targets to approach a therapy of acute inflam ...

Mutations in the LRRK2 (Leucine-Rich Repeat Kinase 2) gene are the most common cause of autosomal dominant Parkinson’s disease. LRRK2 has multiple functional domains including a kinase domain. The kinase activity of LRRK2 is implicated in the pathogenesis of Parkinson’s disease. Devel ...

Class IA phosphoinositide-3 kinases (PI3Ks) signaling has recently emerged as a key element in cancer development because of its ability to trigger a complex panoply of cellular responses controlling survival and proliferation. Many cancers show inappropriately activated PI3K ...

Kinases are members of a major protein family targeted for drug discovery and development. Given the ubiquitous nature of many kinases as well as the broad range of pathways controlled by these enzymes, early safety assessments of small molecule inhibitors of kinases are crucial in identify ...

Polo-like kinase 1 (Plk1) is a key player in mitosis and has been widely recognized as a therapeutic target for many human cancer types. Apart from its kinase domain, Plk1 harbors a protein–protein interaction domain dubbed “polo-box domain” (PBD), by which the enzyme binds to its intracellular an ...

Fast, robust, and inexpensive screening methods are the heart of drug discovery processes. Moreover, it is useful to have access to several established assay formats, for validation purposes. If a targeted protein is an enzyme, the logical and widely used approach is the direct measurement of t ...

Protein kinase inhibitors have emerged as indispensable tools for the elucidation of the biological functions of specific signal transduction pathways and as promising candidates for molecular-targeted therapy. However, because many protein kinase inhibitors are ATP-com ...

The enormous diversity of kinases and their pivotal role in cell signaling have set kinases in the focus of biomedical research. Profiling the kinome of tissues of different origin is essential for biomarker discovery. In drug research, it is necessary to comprehend the specificity profile ...

Because of the limited accessibility of the brain for experimentation, but also for ethical and economical reasons, there is considerable interest in culture models suitable for neurotoxicological research. Although it is generally accepted that in vitro models cannot cover the en ...

It is often necessary to use a variety of techniques to more completely assess a specific area of study. In recent years, this has been increasingly true for the field of neuroendocrinology. Anatomical and molecular methodologies are often used in conjunction with in vitro and in vivo physiolog ...

Advances in molecular genetics over the last decade have resulted in the identification of genetic mutations responsible for several inherited neurological diseases. Not only has cloning of these genes led to methods for diagnosis of patients and identification of carriers but also to ...

Risk assessment has been broadly defined as the characterization of the adverse health effects of human exposures to environmental hazards and can be divided into four major steps: hazard identification, dose-response assessment, exposure assessment, and risk characterizati ...

Over the past decades, the risk assessment of chemicals has frequently been considered a pseudoscientific process, primarily determined by public policy that masquerades as science, rather than representing a process well grounded in firm biological principles. Many toxicolog ...

Homeostasis in neurons is regulated by interactions among many signaling pathways. We will loosely define the term “signaling pathways” to include any molecular mechanisms that transduce external environmental stimuli (e.g., neurotransmitters, hormones, or contact with oth ...