Current Medicinal Chemistry - Volume 12, Issue 25, 2005

To the medicinal chemist uninitiated in the field, inflammation can be an intimidating research area to tackle. There is a bewildering array of prospective targets for antiinflammatory drugs, with countless enzyme inhibitors, receptor antagonists, and other experimental antiinflammatory agents already known. Despite many decades of research, the biology that underpins inflammation, the immune response to infection a Read More

This commentary is an introduction to a special issue on "Latest Developments in the Treatment of Inflammation". It outlines some key events in the inflammatory response to infection or injury and describes some of the important drug targets of relevance to the succeeding articles, which survey inhibitors of these targets as prospective or current antiinflammatory drugs. It also highlights important limitations in the validati Read More

Drugs to treat inflammation are discussed under the following headings: (1) random discoveries covering copper, salicylates, heterocyclic diones, ACTH, adrenal steroids and disease-modifying agents (DMARDs); these include Au(I)-thiolates, chloroquine, and hydroxychloroquine, minocycline, cyclosporin, salazopyrine, D-penicillamine and methotrexate; (2) programmed NSAID developments covering salicylates and fenamates, Read More

Inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis are extremely common in the community, with a prevalence of up to 5%, and they cause substantial morbidity. The development of anti-TNF agents for use initially in rheumatoid arthritis, and subsequently more broadly in inflammatory arthritis, represents the biggest advance in management of these conditions since the i Read More

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory diseases of the central nervous system (CNS) characterized by localized areas with demyelination. Disease is believed to be an autoimmune disorder mediated by activated immune cells such as T- and B-lymphocytes and macrophages/microglia. Lymphocytes are primed in the peripheral tissues by antigens, Read More

TNF-α neutralising agents such as Infliximab (Remicade®), Etanercept (Enbrel®) and the IL-1 receptor antagonist Anakinra (Kineret®), are currently used clinically for the treatment of many inflammatory diseases such as Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis and psoriasis. These protein preparations are expensive to manufacture and administer, Read More

Mitogen-activated protein kinase p38 is a serine/threonine kinase originally isolated from lipopolysaccharide (LPS) stimulated monocytes. There are four isoforms p38α, p38β, p38γ, and p38δ. The most thoroughly studied isoform is p38α, whose activation has been observed in many hematopoietic and nonhematopoietic cell types upon appropriate stimuli. Subsequently, p38α kinase has been shown to be involved in t Read More

The three isotypes of peroxisome proliferator-activated receptors (PPARs), PPARa, β/δ and γ, are ligand-inducible transcription factors that belong to the nuclear hormone receptor family. PPARs are implicated in the control of inflammatory responses and in energy homeostasis and thus, can be defined as metabolic and anti-inflammatory transcription factors. They exert their anti-inflammatory effects by inhibiting the induction o Read More

Phospholipases A2 cleave membrane phospholipids to release arachidonic acid, the precursor to a large family of pro-inflammatory eicosanoids including prostaglandins and leukotrienes that have been proven to exacerbate numerous diseases that have an inflammatory component. Current therapies include NSAIDs' that inhibit cyclooxygenases (COX-1, COX-2) but have no effect on the production of leukotrienes or platelet ac Read More

The focus of this review is on G protein-coupled receptors (GPCRs) for which nonpeptidic ligands are known and have been evaluated for the treatment of inflammatory conditions. GPCRs are the most prevalent class of cell surface proteins in pharmaceutical research today, and GPCR-targeting drugs account for one tenth of worldwide pharmaceutical sales. Of over 800 human GPCRs identified to date, several hundred Read More