Current Medicinal Chemistry - Volume 14, Issue 17, 2007

The endogenous polyamines (spermine, spermidine, and putrescine) are present at relatively high concentrations in the mammalian brain and play crucial roles in a variety of aspects of cell functioning. Stroke is the third most common cause of death and the leading cause of disability among adults in the western world. Brain polyamine levels change dramatically following cerebral ischaemia. Polyamines may be involved in th Read More

One of the outstanding fundamental questions in cancer cell biology concerns how cells coordinate cellular growth (or macromolecular synthesis) with cell cycle progression and mitosis. Intuitively, rapidly dividing cells must have some control over these processes; otherwise cells would continue to shrink in volume with every passing cycle, similar to the cytoreductive divisions seen in the very early stages of embryogene Read More

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hybrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can result in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired si Read More

The hypoxia-inducible transcription factors (HIFs) are central components in the cellular responses to a lack of O2, i.e. hypoxia. Homologs of the HIF system (HIF-1, -2 and -3) are detectable in all nucleated cells of multicellular organisms. Active HIFs are heterodimers (HIF-α/β). In hypoxia the O2-labile α-subunit is translocated to the nucleus where it binds HIF-β. Over 100 HIF target genes have already been identified. The translati Read More

Receptor based QSAR methods represent a computational marriage of structure activity relationship analysis and receptor structure based design that is providing valuable pharmacological insight to a wide range of therapeutic targets. One implementation, called Comparative Binding Energy (COMBINE) analysis, is particularly powerful by virtue of its explicit consideration of interatomic interactions between the ligand and rece Read More

Uric acid is the end-product of purine catabolism. Hyperuricaemia is implicated in disorders such as gout and urolithiasis and recent epidemiological evidence suggests an association between increasing uric acid levels and increased cardiovascular morbidity and mortality. A direct causal role remains to be established but recent studies of losartan, atorvastatin and fenofibrate suggest that uric acid reduction contributes to atte Read More

Cigarette smoking plays a major role in the development of atherosclerosis and is associated with increased morbidity and mortality for coronary heart disease, stroke and peripheral vascular disease. In spite of the abundance of epidemiological evidence that links cigarette smoking to vascular disease, the pathologic mechanisms for such interaction are not clear. The endothelium is a major target organ that undergoes Read More

1α,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] can exert its biological actions through binding with the nuclear vitamin D receptor (VDR), a ligand-activated transcription factor. Next to control of bone and mineral homeostasis, these actions include an immunomodulatory effect and a potent growth-inhibitory, antiproliferative or prodifferentiating action on a wide variety of cell types. The molecular mechanisms underlying this Read More