SBIR Phase I: Near Infrared Substrates for Imaging Autotaxin Activity In Vivo

This Small Business Innovation Research (SBIR) Phase I project aims to synthesize ATXRed, an in vivo imaging agent that is specifically activated by the enzymatic activity of autotaxin. Autotaxin is an extracellular enzyme that generates the phospholipid growth factor lysophophatidic acid (LPA). LPA is involved in a variety of biological functions, such as angiogenesis, wound healing, brain development, immunological competence and the regulation of blood pressure. Both LPA and autotaxin have also been implicated in numerous diseases, especially metastatic cancer. Autotaxin was identified as one of the 40 most induced genes in aggressive breast cancer. The broader impacts of this research are the discovery and commercialization of tools that easily highlight specific biological pathways in living organisms. ATXRed will be welcomed by basic researchers in many fields associated with autotaxin and LPA. However, the utility extends beyond the basic research sphere. ATXRed smart probes could also aid pharmaceutical researchers searching for pharmacological inhibitors of autotaxin and LPA receptor agonists and antagonists. ATXRed would be a powerful tool in many rodent models of human cancer. In vivo autotaxin imaging probes could also aid in the clinic by helping to identify and monitor disease progression and treatment. Ultimately, ATXRed could help guide surgical resection of tumors?tumors previously identified by the smart probe to have elevated autotaxin activity. In total, ATXRed probes have the potential to impact basic research, drug discovery and the clinic as a prime example of molecular medicine applied from bench to bedside.