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Lipid II is an essential component of bacterial cell-wall biosynthesis, and as such is an attractive therapeutic target. Breukink and de Kruijff review the modes of action of compounds targeting Lipid II, and discuss their potential as treatments to combat bacterial infections.
Adenosine receptors have been implicated in the aetiology of various cardiovascular, inflammatory and neurological diseases. Jacobson and Gao review the development and therapeutic promise of agonists and antagonists with high selectivity for each of the four adenosine receptor subtypes.
Advances in microfluidics could prove invaluable both by enhancing existing biological assays and for the design of sophisticated new screens. Dittrich and Manz review current and future applications of scaled-down science and look at the impact of lab-on-a-chip technology on drug discovery.
Gottesman and colleagues review the most common mechanism of resistance to anticancer drugs — drug efflux from cancer cells mediated by ATP-binding cassette (ABC) transporters — and discuss various approaches to combating multidrug resistant cancer, including the development of drugs that inhibit, engage, evade or exploit efflux by ABC transporters.
For many patients with irritable bowel disease, including Crohn's disease or ulcerative colitis, existing therapies are unsatisfactory. Podolsky and Korzenik review progress in the development of new irritable bowel disease drugs including monoclonal antibodies and other biologics, and probiotic and prebiotic strategies.
Two of the newest members of the tumour-necrosis factor family, BLyS and APRIL, are crucial in B-cell development and survival, and are implicated in autoimmune diseases and cancer. Dillon and colleagues review APRIL biology, and compare potential therapeutics that target APRIL and/or BLyS.
Schizophrenia trials are subject to multiple endpoint comparison problems, the risk of false-positives, patient non-compliance, high drop-out rates and missing data. Stroup and colleagues discuss current trial limitations and how these might be addressed by innovations in trial design and statistics.
Pegaptanib, an RNA aptamer that binds to vascular endothelial growth factor, was approved for the treatment of age-related macular degeneration in December 2004, becoming both the first approved aptamer therapeutic and the first anti-angiogenic agent for treating ocular disease.
Excessive glutamate receptor activity, principally of theN-methyl-D-aspartate (NMDA) subtype, contributes to neuronal damage in a large number of neurologic disorders, including dementia. Until recently, however, NMDA receptor antagonists had all failed in clinical trials. Stuart Lipton reviews the mechanism of action that led to the clinical approval of the first NMDA receptor antagonist, memantine, which has become the newest and one of the best-selling drugs for Alzheimer's disease.
Targeting drugs specifically to tumour cells to improve efficacy and reduce toxicity is paramount to the future development of anti-cancer agents. Schrama and colleagues critically review current approaches to achieving this and the status of targeted treatments in development.
Bayesian statistical methods are being increasingly used in clinical research owing to the advantages they can offer compared with conventional approaches. Berry explains the underlying rationale, and discusses the potential of Bayesian trials to improve the effectiveness of drug development.
Cyclooxygenase-2-selective drugs were designed to be safer alternatives to traditional NSAIDs. However, concerns that they increase the risk of thrombotic events have led to the withdrawal of some of these drugs. Mitchell and Warner discuss their underlying mechanisms of actions.
Targeting the epigenetic changes that contribute to tumorigenesis has become an attractive therapeutic strategy. Yoo and Jones review the enzymes involved in epigenetic regulation that are emerging as targets and the numerous drug candidates that are currently being investigated.
Behavioural changes have a major impact on the quality of life of patients with neurodegenerative diseases. Cummings and Zhong discuss how new tools for studying behaviour and improved clinical trial methodologies are facilitating drug development for this large unmet medical need.
