Mini Reviews in Medicinal Chemistry - Volume 5, Issue 9, 2005

Members of the human chemokine family are considered a suitable target for therapeutic intervention, as they have a fundamental role in several important human diseases. Here we outline potential new areas of intervention based on recent findings on chemokine receptor function.

Chemokines belong to a large family of chemoattractant molecules involved in the directed migration of immune cells. They achieve their cellular effects by direct interaction with cell surface receptors. The chemokine receptor CCR1 appears to be involved in a variety of proinflammatory and autoimmune diseases and this makes it a very attractive therapeutic target. This review discusses the identification, chemistry, biology a Read More

The bicyclam AMD3100 (originally called JM3100), in which the two cyclam rings are tethered by an aromatic bridge, emanated from JM2763, where the two cyclam moieties are tethered by an aliphatic linker - JM2763 in turn originated from JM1657, where the cyclam rings are directly linked to one another via a C-C bridge, and which was identified as an impurity, showing anti-HIV activity, in a commercial cyclam prepar Read More

The chemokine family consists of more than 50 structurally-related small proteins which signal through type 1 G-protein coupled receptors (GPCRs) to regulate a range of immune functions, with particular focus on regulating leukocyte trafficking. They have been implicated both in normal physiological leukocyte traffic, and in recruitment of leukocytes to sites of pathological inflammation. As a result, chemokine inhibitors m Read More

Virus-encoded immune evasion mechanisms provide information on viral pathogenesis and offer a unique opportunity to identify new strategies of immune modulation. Secreted proteins that bind a broad range of chemokines have been identified in recent years in poxviruses and herpesviruses. We discuss the properties of these viral chemokine inhibitors and their potential as new therapeutics to treat human infla Read More

The dividing line between essential physiological inflammatory processes and excessive pathological inflammation is often very thin - in some circumstances, indeed, it may be non-existent. Devising anti-inflammatory medications that effectively target only the pathological component therefore remains a central challenge for the pharmaceutical industry. At present, the general rule is that the more powerful the antiinfl Read More

Rheumatoid arthritis and other chronic inflammatory diseases constitute a major therapeutic challenge, usually not sufficiently met by the classical antiinflammatory medications. Recent research efforts provided new insights into the molecular basis of these pathologies and disclosed new opportunities for developing improved drugs directed to the chemical mediators of the disease. The enzyme p38 MAP kinase plays a cen Read More