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

这个小企业创新研究（SBIR）第二阶段项目旨在进一步开发ATX-Red，这是一种体内成像剂，在自分泌运动因子存在下会发出荧光。自分泌运动因子及其产物LPA参与通常涉及细胞运动的许多生物学功能，并且它们的失调与许多疾病相关，包括癌症、纤维化、心血管疾病等。在第一阶段ATX红产生高度翔实的图像在活的生物体，基本上？点亮？肿瘤的在II期研究中，ATX-Red的代谢稳定性将得到改善，性能也将得到提高。ATX-Red将被用于监测小鼠乳腺癌和肺纤维化的进展和治疗。这项研究的更广泛影响是改善基础研究，药物发现，临床诊断和疾病治疗，最终结果是改善人类健康。ATXRed将成为与自分泌运动因子和LPA相关的许多基础研究领域不可或缺的工具，在该工具开发之前，关于体内自分泌运动因子的问题基本上是无法回答的。除了在研究竞技场中的使用外，ATX-Red还将有助于治疗学的发展。目前正在努力开发靶向自分泌运动因子途径的药物。ATX-Red将可能用于开发这些化合物所需的广泛体内实验。人类患者也将从这项研究中受益，因为ATX-Red可以作为靶向与自分泌运动因子失调相关疾病的药物的伴随诊断。进一步的临床应用可能包括诊断疾病，甚至指导肿瘤的手术切除。

This Small Business Innovation Research (SBIR) Phase II project aims to further develop ATX-Red, an in vivo imaging agent that becomes fluorescent in the presence of the enzyme autotaxin. Autotaxin and its product LPA are involved in numerous biological functions that generally involve cell movement, and their dysregulation is associated with many diseases including cancer, fibroses, cardiovascular disease, and others. In Phase I ATX-Red generated highly informative images in living organisms, essentially ?lighting up? tumors. In Phase II ATX-Red metabolic stability will be improved and increased performance will be demonstrated. Then ATX-Red will be used to monitor progression and treatment of breast cancer and pulmonary fibrosis in mice.The broader impacts of this research are improvements to basic research, drug discovery, clinical diagnosis and disease treatment, with the ultimate result being an improvement to human health. ATXRed will be an indispensible tool to the many basic research fields associated with autotaxin and LPA, where questions regarding autotaxin in vivo were essentially unanswerable prior to the development of this tool. In addition to its usage in the research arena, ATX-Red will aid development of therapeutics. Currently significant efforts are underway to develop drugs targeting autotaxin pathways. ATX-Red will likely be employed in the extensive in vivo experimentation needed to develop these compounds. Human patients also stands to benefit from this research, since ATX-Red could act as a companion diagnostic for pharmaceuticals targeting diseases associated with autotaxin dysregulation. Further clinical applications might include diagnosing disease and even directing surgical resection of tumors.