Current Pharmaceutical Design - Volume 10, Issue 12, 2004

This issue of Current Pharmaceutical Design is dedicated to delivery of therapeutics to the central nervous system (CNS). Some of the most devastating diseases facing mankind are those of the CNS. A great number of substances are candidates for treatment of CNS diseases, but therapeutic development in this area faces a special challenge: the blood-brain barrier (BBB). Almost as great as the actual BBB, is the b Read More

This issue of Current Pharmaceutical Design is dedicated to the characterization of potential anticancer agents. In this respect, a plethora of approaches are currently being investigated to design or discover novel compounds that are capable to effectively and selectively kill cancer cells, sparing normal cells. These approaches vary from the selection of possible cancer-specific protein targets and the design and synthesis Read More

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) form a very effective barrier to the free diffusion of many polar solutes into the brain. Many metabolites that are polar have their brain entry facilitated by specific inwardly-directed transport mechanisms. In general the more lipid soluble a molecule or drug is, the more readily it will tend to partition into brain tissue. However, a very significant Read More

The introduction, in 1995, of highly active antiretroviral therapy (HAART) dramatically reduced the morbidity and mortality of HIV-infected patients. However, the brain remains a site of viral replication for HIV and thus is still an important target for antiretroviral agents. Consequently, a clear understanding of how the current anti-HIV drugs reach the CNS, and interact at the level of the blood-brain barrier and blood-CSF barrie Read More

In recent years, VIP / PACAP / secretin family has special interest. Family members are vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, glucagon, glucagon like peptide-1 (GLP1), GLP2, gastric inhibitory peptide (GIP), growth hormone releasing hormone (GHRH or GRF), and peptide histidine methionine (PHM). Most of the family members present both in central nervous Read More

Brain tumors are one of the most lethal forms of cancer. They are extremely difficult to treat. Although, the rate of brain tumor incidence is relatively low, the field clearly lacks therapeutic strategies capable of overcoming barriers for effective delivery of drugs to brain tumors. Clinical failure of many potentially effective therapeutics for the treatment of brain tumors is usually not due to a lack of drug potency, but rath Read More

The blood-brain barrier (BBB) efficiently restricts penetration of therapeutic agents to the brain from the periphery. Therefore, discovery of new modalities allowing for effective delivery of drugs and biomacromolecules to the central nervous system (CNS) is of great need and importance for treatment of neurodegenerative disorders. This manuscript focuses on three relatively new strategies. The first strategy involves inhibiti Read More

Most drugs with central nervous system (CNS) activity enter the brain either by diffusing across the membranes which comprise the blood-brain barrier (BBB) or by being transported by carrier systems across those membranes. Substances which cannot cross the BBB by one of these mechanisms, like serum albumin, are virtually excluded from the CNS. However, this exclusion is not absolute. Cerebrospinal fluid (CSF) l Read More

Protein kinase C (PKC) isozymes (α, βI, βII, γ, δ, ε, η, Θ) are major receptors of tumor promoters and also play a crucial role in cellular signal transduction via the second messenger, 1,2-diacyl-sn-glycerol (DG). Each isozyme of PKC is involved in diverse biological events, indicating that it serves as a novel therapeutic target. Since PKC isozymes contain two possible binding sites of tumor promoters and DG (C1A and C1B d Read More

Amongst the most promising chemopreventive agents, certain natural polyphenols have recently received a great deal of attention from the scientific community, nutritionists, the pharmaceutical industry and the public, due to their demonstrated inhibitory activity against tumorigenesis. In view of their anticancer properties, these compounds also hold great promise as potential chemotherapeutic agents. However, to tra Read More

The tumor cell growth inhibitory activities (log 1 / GI50) of 166 anticancer agents studied at the National Cancer Institute (NCI) in vitro anticancer screening program have allowed us to analyze the relative importance of physicochemical parameters in influencing the inhibitory activities. Increased molecular weight, as measured by the logarithm of molecular weight (log MW), is found to be an important contributor to the Read More

Many natural and synthetic compounds bind to tubulin, an ubiquitous globular protein that provides the building blocks for the cellular microtubule network that controls chromosome segregation during mitosis, vesicle movements, intracellular transport of organelles, ciliar and flagellar movement, and maintenance of cell shape. Since the isolation of the antimitotic marine natural product curacin A in 1994, synthetic wor Read More