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

这个小型企业创新研究(SBIR)第一阶段项目旨在合成ATXRed，这是一种体内显像剂，专门由自体趋化素酶活性激活。自体趋化蛋白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、免疫功能和血压调节。LPA和自体趋化蛋白也与许多疾病有关，特别是转移性癌症。Autoaxin被确定为侵袭性乳腺癌中诱导作用最强的40个基因之一。这项研究的更广泛的影响是发现并商业化了一些工具，这些工具可以轻松地突出活体中的特定生物路径。ATXRed将受到与自体分类素和LPA相关的许多领域的基础研究人员的欢迎。然而，这种效用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自体趋化素和LPA受体激动剂和拮抗剂的药理抑制剂。在许多人类癌症的啮齿动物模型中，ATXRed将是一个强大的工具。体内的自体趋化蛋白成像探针也可以帮助识别和监测疾病的进展和治疗，从而有助于临床。最终，ATXRed可以帮助指导肿瘤的手术切除--以前被智能探针识别为具有升高的自体趋化蛋白活性的肿瘤。总而言之，ATXRed探针有可能影响基础研究、药物发现和临床，成为分子医学从工作台到床边应用的典型例子。

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.