This Small Business Innovation Research (SBIR) Phase I project has the goal of developing a technology that accelerates the discovery of drugs for a broad range of diseases. The proposed technology, termed SAMDI, is innovative in that it combines advances in materials science and mass spectrometry to allow the rapid testing of potential drug candidates. The technology uses robotic liquid handling and high-density assay plates that are modified with substrate molecules that are modified by enzymes that alter the structures of the molecules. This change in structure is characterized by mass spectrometry and provides a simple assay for the enzyme activity. The SBIR project will translate the SAMDI assay to a high throughput format that can assay many thousands of samples in a day in an automated fashion.
The broader/commercial impacts of this research are expected in the early stages of drug discovery. The development of a drug begins with a screen, where hundreds of thousands of small drug-like compounds are tested to identify those few that can interact with and alter the activity of an enzyme that is involved in disease progression. These ?hits? are then optimized and ultimately lead to pharmaceuticals that benefit patients. For many enzymes, assays that are rapid, cost-effective and reliable do not yet exist and therefore delay the drug discovery process. The SAMDI assay is applicable to most of these difficult targets and would radically accelerate drug discovery programs for a broad range of diseases.
New drugs for the treatment of human diseases begin their 10-12 year journey to market with the drug discovery stage. This stage often entails screening millions of small drug-like chemicals that specifically inhibit a biological activity that causes disease. Activity is commonly surveyed in thousands of biochemical reactions in a process called high-throughput screening (HTS). HTS is used as a means of finding the proverbial "needle in a haystack" molecule that has a 1 in 5,000 chance of making it to market. The drug discovery process is littered with molecules that fail to have the desired drug-like properties or activity. The presence of false positive activity is one way these molecules fail to continue through the drug development pipeline. False positives are inherent in the HTS process, and limiting these undesired results can significantly increase the efficiency of successful drug discovery. SAMDI Tech Incâ€™s Small Business Innovation Research (SBIR) Phase I project had the goal of developing a high throughput drug discovery tool, called SAMDI. SAMDI has the capability of surveying many different biological activities and reducing false positive rates, thereby increasing the efficiency of drug discovery. SAMDI Techâ€™s unique label-free drug discovery technology can ultimately be applied to a wide variety of drug targets that are novel or those for which activity is difficult to assay. We have demonstrated the utility of SAMDI through the discovery of inhibitors to a drug target, HDAC8, that is difficult to assay with conventional technologies. In short, development of the SAMDI platform will ultimately expedite the discovery process of new therapeutics. This in turn will assist in maximizing the number of new drugs in the clinic for treatment of diseases.