A novel computational drug repurposing approach for Systemic Lupus Erythematosus (SLE) treatment using Semantic Web technologies

摘要

Development of new drugs is costly, time-consuming, and achieves only a minor success rate (Morgan et al. 2011; Kesselheim, Avorn, and Sarpatwari 2016). The traditional approach could potentially take up to 15 years to complete clinical testing and gain authority approval. Furthermore, the failure rate of new drugs is about 95%, and each one that makes it to final approval has an estimated cost of $1 billion (Morgan et al. 2011; Kesselheim, Avorn, and Sarpatwari 2016; Collins 2011). Therefore, there is an urgent need to both reduce costs and accelerate the drug development process while also increasing the success rate for newly-developed drugs. As such, a new approach is vital. This can begin with methods for re-inventing existing drugs by screening them for new indications for either common or rare diseases. ‘Drug repositioning’ or ‘drug repurposing’ has emerged as a prospective approach for helping the bio-pharmaceutical industry, with a primary focus on improving the business of pharmaceuticals and a secondary focus on improving the therapeutic aspect of the industry (Sardana et al. 2011; Ashburn and Thor 2004). Conceptually, drug repurposing is the process of finding and developing new uses for pre-existing drugs, applying them to functions other than the diseases they were originally geared towards (Ashburn and Thor 2004). This strategy relies on having approved compounds with well-characterized pharmacology, which are thus already associated with a safety profile, allowing the time frame for approval to be substantially reduced relative to novel drug development. It is therefore not surprising that among new medications in 2009 (including vaccines and new formulations), 51 were repositioned drugs, and those represented 30% of all approved drugs brought to market that year (Sardana et al. 2011; Graul and Cruces 2011). Moreover, the profits realized from drug repurposing could exceed billions. For instance, an initial attempt in repurposing thalidomide has led to it now being used for multiple myeloma, reaching profits of $272 million in 2003(Singhal et al. 1999); it also has recently been approved by the United States as a treatment for Type 2 Diabetes due to having dopamine agonist properties similar to bromocriptine (Pijl et al. 2000).