Mini Reviews in Medicinal Chemistry - Volume 6, Issue 8, 2006

Type 2 diabetes is a complex metabolic disease with hyperglycemia as its recognizable hallmark. Hepatic glucose output is elevated in Type 2 diabetic patients, and evidence suggests drugs which lower hepatic glucose production are effective antihyperglycemic agents. Glycogenolysis, which is the release of monomeric glucose from its polymeric storage form called glycogen, is a key contributor to hepatic glucose outp Read More

Factor Xa (fXa) is the vitamin K-dependent serine protease of the prothrombinase complex (fXa, factor Va, negatively charged membrane, and calcium) which is responsible for the conversion of prothrombin to thrombin in the final stage of the coagulation cascade. The proteolytic activity of fXa in plasma is primarily regulated by three physiological inhibitors, antithrombin (AT), protein Z-dependent protease inhibitor (ZPI) and Read More

The importance of p38 MAPK inhibitors as new drug for rheumatoid arthritis is reflected by the large number of compounds that has been developed over the last years. In this review new insights such as non-stressful activation of p38 MAPK, and the role of p38 MAPK in regulation of NF-κB recruitment are also discussed.

Hibernation is a unique phenotype displayed by a phylogenetically diverse group of organisms including several species of mammals and one species of primate. Here we review evidence for blood and tissue borne signaling molecules in hibernating animals, achievements in isolating and characterizing these molecules, and potential medicinal applications.

Based on their mechanism of action, anti-tumor drugs that target the cell cycle can be generally divided into three categories, namely, blocking DNA synthesis, causing DNA damage, and disrupting mitotic processes. In terms of mitotic inhibitors, most compounds used in the clinic impair the normal function of mitotic spindles by targeting tubulins, basic building blocks of microtubules. In vivo, these compounds often exhibit si Read More

Obesity is a state of leptin resistance in which the membrane leptin receptor and the JAK-STAT pathway are blocked. This leads to increased intracellular concentrations of lipid metabolites, increased non-oxidative metabolism by adipocytes, and stimulation of the cell estrogen cycle. These factors are potentially oncogenic via the shared mitogen-activated protein kinase (MAPK), mitogen/extracellular signal-regulated Read More

Surface (S)-layer proteins and S-layer fusion proteins incorporating functional sequences, self-assemble into monomolecular lattices on solid supports and on various lipid structures. Based on these S-layer proteins, supramolecular assemblies can be constructed which are envisaged for label-free detection systems, as affinity matrix, as anti-allergic immuno-therapeutics, as membrane protein-based screening devices, an Read More

The carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous zinc enzymes which catalyze a very simple physiological reaction, the interconversion between carbon dioxide and the bicarbonate ion, and are involved in physiological and pathological processes. The different isozymes have been considered as important targets for inhibitors with clinical applications. Several sulfonamide carbonic anhydrase inhibitors (CAIs) were u Read More

Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are the principal regulators of drug/xenobiotic disposition and toxicity. These nuclear receptors display considerable cross-regulation of their target genes, and species-specific, yet promiscuous activation by a large number of structurally dissimilar ligands. Activation of PXR and/or CAR will frequently result in enhanced drug metabolism, disturb Read More

NF-κB is a ubiquitous and well-characterised protein responsible for the regulation of complex phenomena, with a pivotal role in controlling cell signalling in the body under certain physiological and pathological conditions. Among other functions, NF-κB controls the expression of genes encoding the pro-inflammatory cytokines (e. g., IL-1, IL- 2, IL-6, TNF-α, etc.), chemokines (e. g., IL-8, MIP-1α, MCP1, RANTES, eotaxin, et Read More