Current Pharmaceutical Design - Volume 10, Issue 11, 2004

Activating mutations of FLT3 (FMS-Like Tyrosine kinase-3) are the most common molecular abnormality in acute myeloid leukemia (AML). Their presence is associated with a worse prognosis, and the recognition of this has led to the development of several new small molecule FLT3 tyrosine kinase inhibitors. In this review, we summarize these developments and compare and contrast these novel agents both with regards to t Read More

Acute graft-versus-host disease (GVHD) and chronic GVHD remain the major barriers to successful hematopoietic cell transplantation. The induction of GVHD may be divided into three phases- (I) recipient conditioning, (II) donor T cell activation, and (III) effector cells mediating GVHD. Cytokines have been shown to be extremely important in the initiation and propagation of GVHD. Of note, IL-2 and TNF-α lead to cellular Read More

Harnessing the power of the immune system to eliminate infection and cancer is a long-standing goal in clinical immunology. The development of a robust immune response to foreign antigen relies, in part, on communication between cellular components of the immune system. The proteins involved in governing the magnitude and longevity of an immune response are collectively called cytokines. Cytokines act directly on im Read More

Angiogenesis is defined as the formation of new capillaries from prexisting blood vessels and plays an important role in the progression of solid tumors and hematologic malignancies. Markers of angiogenesis correlate with clinical characteristics in leukemia and non-Hodgkin´s-lymphoma, serving as predictors of poor prognosis. Antiangiogenic effects of chemotherapeutics as well as of novel drugs such as farnesyltransfera Read More

Recombinant protein technology produces drugs for human therapy in unprecedented quantity and quality. Research is now focusing on the relationship between pharmacokinetic and pharmacodynamic properties of molecules, with the aim of engineering proteins that possess enhanced therapeutic characteristics in contrast to being used as simple replacements for the natural equivalent. The addition of a polyethylene gl Read More

SDF-1 and CXCR4 are an important chemokine ligand / receptor pair, which play a crucial role in numerous biological processes including hematopoiesis, cardiogenesis, vasculogenesis, neuronal development and immune cell trafficking. They have also been implicated in various pathological conditions such as cancer, infection with the human immunodeficiency virus (HIV) and various inflammatory conditions. Nu Read More

Various growth factors such as the platelet derived growth factor (PDGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) transduce their mitogenic signals through the activation of tyrosine kinase receptors (RTKs). Since enhanced RTK activity has been associated with the development of proliferative diseases such as atheroscleros Read More

Designing biologically active chemicals and managing their risks requires a holistic perspective on the chemical-biological interactions that form the basis of selective toxicity. The balance of therapeutic and adverse outcomes for new drugs and pesticides is managed by shaping the probabilities for transport, metabolism, and molecular initiating events. For chemicals activated as well as detoxified by metabolism, selective toxicity Read More