The main concept behind drug repurposing is that novel drug indications can be identified based on the protein

In contrast, the primary protein sequence is in many cases only a partial or no reliable predictor for protein structure. In this sense, the analyses presented here represent an opportunity where comprehensive subcellular localization data is available to assess the reliability of redundancies predicted by sequence homology. The 25 cell types and tissues used for our expression analysis are not representative or comprehensive, but chosen only for discernability in the binary analysis. Hence, a similarity score of 80% based on a score of ‘20’ cannot be compared as an absolute number, but only relative to the same criteria for other rabs. Neither cellular expression nor the subcellular localization criteria are sufficient to assess potential redundancy. For example, both rab3 and rabX4 are identically pan-neuronally expressed, but Rab3 marks synaptic vesicles whereas RabX4 marks Rab11-positive compartments. Conversely, rab21 and rabX4 have substantially different expression patterns, yet when they overlap in the nervous system they exhibit the identical subcellular localization profile. Hence, these two rab GTPases are potential candidates for similar or redundant functions in these cells only. More generally, in the pair-wise comparison a rab GTPase with restricted expression receives a low score when compared to a rab GTPase with broader expression, and hence will be categorized as less similar. However, this lower score does not correlate with the probability of redundancy in the cell types where the two rab GTPases are actually co-expressed. We therefore regard the combination of cellular and subcellular profile similarities as a means to restrict the number of potentially redundant rab GTPases. Importantly, all our rab-Gal4 lines represent targeting vectors for the generation of molecularly defined mutants through ends-out homologous recombination, as demonstrated in our original studies. Hence, the completed rab-Gal4 kit provides all ARRY-142886 MEK inhibitor necessary tools to experimentally test functional predictions from our analyses, as well as experiments using double and triple mutants to verify such functional relationships. The current model of drug discovery and development is perceived as a costly and time-consuming process. To reduce the cost and shorten the duration for drug development, drug repurposing, also known as drug repositioning, has become an attractive alternative to traditional drug development aiming to shorten the development process. Drug repurposing is the process of finding a new indication for existing drug compounds. In other words, it is a discovery process on how an existing drug compound can be used for the treatment of diseases other than its original indication. Reusing these drug compounds has the advantage of bypassing many of the expensive steps of drug development, such as in vitro and in vivo screening, chemical optimization, toxicology, bulk manufacturing, formulation development. This reduces cost and development risks, as well as shortens the typical 10–17 year process of drug development to 3–12 years. The best known success story of drug repositioning is the development of sildenafil, a compound that was developed by Pfizer and intended for the treatment of angina. Clinical trials of the drug showed unexpected side effects that led to the treatment of erectile dysfunction, and sildenafil became the blockbuster drug more commonly known as ViagraH. Further studies and repositioning of the drug compound showed yet another therapeutic indication for treating pulmonary arterial hypertension, marketed as RevatioH. This is due to the fact that sildenafil is an inhibitor of phosphodiesterase-5 proteins, and PDE-5 is known to be expressed in pulmonary hypertensive lungs.