Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 6, Issue 1, 2007

Whereas G protein-coupled and nuclear receptors have been in the focus of the pharmaceutical industry since decades, protein kinases became interesting drug targets more recently. Several protein kinase inhibitors are well established for the treatment of tumors in the meantime, many more are in clinical development. Inside into the biology of protein kinases and progress in technologies to target these molecules, howe Read More

Protein kinases are key factors in signal transduction, playing a pivotal role in the initiation, propagation and regulation of immunologic responses. In contrast to protein- protein interaction they are considered to be “drugable” by small molecular weight inhibitors. Thus kinases moved into in the focus as promising drug targets for the therapy of inflammatory and autoimmune diseases. Whereas some kinase inhibitors are in clinic Read More

Protein kinases are major drug targets in pharmaceutical companies. A deep understanding of the features of the ATP binding niche is of utmost importance for the assessment of drugability and selectivity. This article focuses on recent developments in experimental and theoretical methods relating to structural aspects of drugability and selectivity. Predicting drugability is enabled by a detailed analysis of the structural charac Read More

Inflammation seems to be at the beginning of the majority of chronic diseases, and major efforts are dedicated to the development of anti-inflammatory drugs. Chronic inflammatory diseases, such as psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease and asthma, are diseases that affect a large segment of our population. Recent evidence suggests that even metabolic diseases, such as type 2 diabetes, Read More

Dysregulated protein kinase activity can cause severe human diseases. Consequently, there is a growing number of kinases that constitute candidate targets for pharmaceutical intervention. However, target validation is critical, since not all kinases are “druggable”, i.e. suitable as a selective drug target. In this review, we briefly introduce major strategies for generating mouse models to analyse and control the expr Read More

Tyrosine kinases play key roles in cell proliferation, differentiation, survival, cell migration, tissue development, and cell metabolisms. Mutation and /or truncation in tyrosine kinases result in their constitutive activation independent of ligand stimulation. The constitutively activated tyrosine kinase often triggers cancer development. Furthermore, it is well documented that overexpression of tyrosine kinases is involved in malignancy Read More

A variety of different cell lineages of the hematopoietic system are activated during inflammatory processes. These cells not only contribute to the beneficial outcome of an immune response, but can also cause pathology such as autoimmunity as a consequence of extended or uncontrolled reactions. Therefore, an understanding of the basic mechanisms that lead to immune cell activation and the identification of key molecu Read More

The signal transduction pathways leading to activation of Jun-NH2-terminal kinase (JNK) and nuclear factor- κB (NF-κB) are activated by a plethora of extracellular signals. Small molecules have been developed that inhibit the JNK or IκB protein kinases. Additionally, several cell-penetrating peptides have been characterized that disrupt proteinprotein interaction domains within the NF-κB and JNK signalling pathways. Usually Read More

Sequential activation of kinases (protein kinase cascades) is a general mechanism of signal transduction in many cellular processes. Several related intracellular signaling cascades have been found and characterized in the last 25 years known as mitogen-activated protein kinase (MAPK) signaling cascades. These cascades cooperate in transmitting extracellular signals to their intracellular targets and thus initiate cellular processes Read More