New anti malarial drugs are needed urgently. selleck compound Recent improvements in cell based screening technology have led to over 20,000 new starting points in medicinal chemistry, and the great majority of these data are open access. This has led to a whole series of new mole cules in preclinical development. For example, one series, the spiroindolones, has entered early clinical studies only five years after the initiation of screening. In general, however, malaria projects take much longer than five years to go from discovery to having a clinical candidate. Sometimes this is because of technical chal lenges, but more often because of lack of funding or other resources and the attrition rates are high. It is clearly important to search for new approaches to make this process more efficient.

An alternative approach is that of drug repositioning or repurposing. Most simply, this is taking a molecule that has been developed for one indication and showing its utility in another. Although the concept is widely discussed as an attractive drug development strategy, meaningful published data on its success rate and the factors determining that success are limited. Starting with a molecule that has already undergone clinical trials in another indication provides several potential advantages. The clinical safety profile will be understood, and safe therapeutic doses will have been established. Importantly, human pharmacokinetic data will exist and provide some indication of whether thera peutic concentrations in the new indication can be achieved safely and maintained in patients.

In addition, there are regulatory fast track processes, such as the US Food and Drug Administration 505 process, where the applicant can rely on data from the studies done by others to progress the compound for the new indication. This has acted as a spur to finding new activities of old molecules. Programmes to identify new clinical activities of existing medicines have been conducted in many therapeutic areas, such as oncology and for orphan diseases, where there is often an extremely high and specific unmet medical need. Approaches have also been successful in in fectious disease, such as tuberculosis, schistosomiasis and onchocerciasis. In human African trypano somiasis, fexinidazole was not so much repositioned as rediscovered following compound mining efforts of more than 700 new and existing nitroheterocycles.

efficacy in animal models was initially reported in the 1980s. In malaria, there have also been initiatives in drug repositioning. Screening a library of 2,687 compounds containing 1,937 FDA registered medicines and 750 other molecules in clinical development identified astemizole as the most promising compound, with good activity against P. falciparum Anacetrapib blood stages.