Current Drug Discovery Technologies - Volume 5, Issue 1, 2008

Selective activation of blood coagulation in tumor vessels with subsequent thrombosis and tumor infarction is a promising strategy in cancer therapy. To this end, different fusion proteins consisting of the extracellular domain of tissue factor (truncated tissue factor, tTF) were fused to the peptides GRGDSP (abbr. RGD), GNGRAHA (abbr. NGR) or cyclic derivates of these peptides, which selectively target αv-integrins or amin Read More

In recent years, significant progresses have been achieved in clinical oncology due to a plethora of new chemotherapeutic drugs and agents for targeted therapy. However, clinical response and overall survival rates have not improved significantly for a large number of different tumors. This may at least in part be due to the enormous genetic heterogeneity among tumors, even within a tumor entity. Moreover, besides individ Read More

Despite recent advances in the diagnoses and treatment of breast cancer, this disease continues to be a major cause of death. One of the biggest challenges in breast cancer treatment is bone metastasis. Breast cancer cells (BCCs) are capable of migrating to the bone marrow and utilizing the marrow microenvironment to remain quiescent. While exhibiting quiescence in the marrow, BCCs can evade the effects of conventional Read More

Components of the cell-surface and extracellular matrix (including cell walls of some microorganisms) present ideal but often challenging targets for disease detection and targeting. In the past few years, selection of peptide and oligonucleotide biomimics against secreted and extracellular targets has resulted in the isolation of small high affinity binding agents against target molecules. However, little attention has been paid Read More

The Toll-like receptor (TLR) family plays a fundamental role in host innate immunity by mounting a rapid and potent inflammatory response to pathogen infection. TLRs recognize distinct microbial components and activate intracellular signaling pathways that induce expression of host inflammatory genes. Extensive research in the past decade to understand TLR-mediated mechanisms of innate immunity has enabled p Read More

Site-specific drug delivery to bone is considered to be achievable by utilizing acidic amino acid homopeptides. We found that fluorescence-labeled acidic amino acid (L-Asp or L-Glu) homopeptides containing six or more residues bound strongly to hydroxyapatite, which is a major component of bone, and were selectively delivered to and retained in bone after systemic administration. We explored the applicability of this result fo Read More

MicroRNAs (miRNAs) are endogenous, short, double-stranded and noncoding RNA molecules that have been identified in a variety of organisms and certain viruses. This group of new molecules is transcribed mainly from the introns and/or exons or intergenic regions and plays important regulatory roles in development and gene expression. Mature miRNAs are typically 20-24 nucleotides in length and regulate target mRN Read More

The rapidly growing interest in kinases as drug targets has prompted the development of many kinase assay technologies. These technologies can be grouped into three categories: radiometric assays, phospho-antibody-dependent fluorescence/luminescence assays, and phospho-antibody-independent fluorescence/luminescence assays. This article will review some of the major kinase assay technologies on the market, with Read More

Ligand-bound and free structures of brain membrane targets for L-glutamate (Glu) suggest the view, that quaternary rearrangements are associated with ligand binding. Rearrangement of the machinery of the signaling apparatus, such as molecular switches, recognition sites and the target structures for ligand binding of Glu-operated ion channel and heptahelical G-protein-coupled family receptors have been quantifie Read More

Accumulating evidence implicates a failure of myelin-reactive immune cells to undergo apoptosis in the pathological events contributing to multiple sclerosis (MS). We have recently demonstrated that members of the inhibitor of apoptosis (IAP) family of antiapoptotic genes are elevated in peripheral blood immune cells (monocytes, T cells) of patients with aggressive forms of MS (secondary progressive) or those with relapsi Read More

Growth factor-activated receptor tyrosine kinases (RTKs) undergo rapid endocytosis and degradation in lysosomes. This process, known as receptor downregulation, is essential to prevent the overgrowth of cells by terminating signal transduction from activated RTKs. Thus, defects in RTK downergulation lead to cell proliferative disorders such as cancer. Upon endocytosis, RTKs are delivered to endosomes, from where the Read More