Current Pharmaceutical Design - Volume 10, Issue 16, 2004

The hematopoietic class III receptor tyrosine kinase (RTK) Flt3 (Flk2, STK1) has recently received much attention as a potential drug target. Activation of Flt3 by different types of mutations plays an important role for proliferation, resistance to apoptosis, and prevention of differentiation of leukemic blasts in acute myeloid leukemia (AML). At least one type of such mutations - an internal tandem duplication in the Flt3 juxta Read More

MAPK (Mitogen Activated Protein Kinase) pathways mediate fundamental biological processes and have moved into the limelight of drug discovery during the past decade. Here we review the biochemistry and biology of MAPK signalling with a focus on ERK, JNK and p38. We summarise current drug discovery efforts and clinical trials. Further, we critically discuss the rationale behind current strategies of using MAPK pathways as Read More

The Ras-Raf-MEK-ERK intracellular signaling cascade can be activated in response to a variety of extracellular stimuli. Growth factor binding to extracellular receptors results in activation of Ras, which in turn interacts with and activates Raf, leading to the phosphorylation of the dual specificity kinase MEK (MAP kinase kinase) on two distinct serine residues. MEK possesses a number of unique biochemical and biologica Read More

Phosphoinositide 3-kinases (PI3K) represent a family of intracellular signaling proteins, which control a variety of important cellular functions such as proliferation, apoptosis and migration. Recent findings suggest an involvement of PI3K in the pathogenesis of numerous diseases including cancer, heart failure and autoimmune / inflammatory disorders. This review summarizes the current knowledge of the emerging therap Read More

As our understanding of tumorigenesis increases, interference with the various signaling pathways of tumor cells has become an attractive approach to arresting tumor cell growth and overcoming chemoresistance. Among many intracellular signaling proteins, protein kinase C (PKC) isoenzymes have been identified as possible targets to render tumor cells more susceptible to apoptosis and growth arrest. We review t Read More

In recent years, new strategies in cancer therapy have been developed targeting key signaling molecules in the receptor tyrosine kinase signal transduction pathway. In contrast, most therapeutical concepts to manipulate G protein-coupled receptors (GPCR)-mediated disorders are still limited to the use of receptor-specific agonists or antagonists. Visible progress in the understanding of GPCR signaling complexity, especi Read More

Gene expression profiling has become a versatile tool for biomedical research, which allows the assessment of a wide variety of basic questions in cellular regulation, in particular when a large number of molecular parameters have changed. There are various applications in drug research for which gene expression profiling is a very suitable approach. This includes: target identification, target validation, validation of drug speci Read More

Reducing tumor load by therapeutic induction of cell death in the transformed phenotype is the desirable goal of most chemotherapeutic regimens. Despite the tremendous strides made in our understanding of mechanisms that endow tumor cells with the ability to evade execution signals, development of chemo-resistance is still a major obstacle in the successful management of the disease. A host of factors have been im Read More

Basic studies on angiogenesis in normal and pathologic conditions, as well as research on drugs or genes / proteins that stimulate or regulate the angiogenic process, can rely on an increasing number of experimental models. Among non-mammalian models, Zebrafish is adopted by an increasing number of research groups. Moreover, angiogenesis and vasculogenesis in invertebrates like the leech Hirudo medicinalis sh Read More