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

这个小企业创新研究（SBIR）第一阶段项目旨在合成ATXRed，这是一种体内成像剂，由autotaxin的酶活性特异性激活。自分泌运动因子是一种产生磷脂生长因子溶血磷脂酸（LPA）的胞外酶。LPA参与多种生物学功能，如血管生成、伤口愈合、脑发育、免疫能力和血压调节。LPA和自分泌运动因子也与许多疾病，特别是转移性癌症有关。Autotaxin被确定为侵袭性乳腺癌中40个最易诱导的基因之一。这项研究的更广泛影响是发现和商业化的工具，很容易突出活生物体中的特定生物学途径。ATXRed将受到与autotaxin和LPA相关的许多领域的基础研究人员的欢迎。然而，实用性超出了基础研究领域。ATXRed智能探针还可以帮助制药研究人员寻找autotaxin和LPA受体激动剂和拮抗剂的药理学抑制剂。ATXRed将成为许多人类癌症啮齿动物模型的有力工具。体内自分泌运动因子成像探针也可以通过帮助识别和监测疾病进展和治疗来帮助临床。最终，ATXRed可以帮助指导肿瘤的手术切除？先前通过智能探针鉴定的肿瘤具有升高的自分泌运动因子活性。总的来说，ATXRed探针有可能影响基础研究，药物发现和临床，作为分子医学从实验室应用到临床的一个典型例子。

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.