I-Corps: New Methods in Plant-Based Drug Discovery

一场严重的全球医疗危机正在推动人们寻找新的治疗方法来治疗耐药微生物、侵袭性癌症和日益流行的自身免疫性疾病。 为了提供这些新的疗法，制药公司需要一种经济的新型生物活性化合物来源来驱动其产品线。这个I-Corps团队将从濒危植物产品中提供这些新化合物，这些产品由于其保护状态而未被触及。 这一新概念不仅具有开发广泛的天然产物衍生疗法的巨大潜力，而且可持续的植物培养方法也将促进我们对有效保护这些濒危物种的理解。 在实验室环境中与这些植物合作，使科学家能够对植物施加压力，以最大限度地生产防御化合物。 植物的这些免疫反应化学物质在其自然环境中可能无法检测到，但正是这些化合物具有最大的生物活性潜力。濒危植物，由于其灭绝的风险，很少被筛选出生物活性化合物。筛选这些新植物将是该公司的主要重点，但同样的技术将为濒危植物的保护和可持续利用提供协议。这个I-Corps团队通过与田纳西州植物医学研究中心的合作，开发和优化了筛选和分离方法，以成功测试这种概念验证。最初筛选粗提取物的传统方法可能会错过微量活性化合物，例如信号分子，但该团队正在开发的方法将有效地将来自不同压力源的提取物分解为5至10种化合物/样品。这些样品将在96孔板中进行初步筛选，以确定其在抗微生物、抗癌和抗炎生物测定中的活性。感兴趣的样品将被进一步分级分离为纯化合物，并重新筛选以鉴定活性化合物。这种新型的药物线索管道对于与制药公司的潜在合作伙伴关系和许可证将非常有吸引力，同时该团队继续开发高影响力的线索。任何进入市场的铅都将对患者及其家人的生活产生巨大影响。

A serious global healthcare crisis exists that is driving the search for new treatments for drug resistant microbes, aggressive cancers, and an increasing prevalence of autoimmune diseases. To provide these novel therapies, pharmaceutical companies need an economical source of novel bioactive compounds to drive their product pipelines. This I-Corps team will provide these new compounds from endangered plant products that have remained untouched due to their conservation status. This novel concept not only has excellent potential for developing a broad spectrum of natural product derived therapeutics, but sustainable plant culture methods will also advance our understanding of effective conservation efforts to protect these endangered species. Working with these plants in a laboratory environment allows scientists to stress the plants to maximize the production of their defensive compounds. These immune response chemicals of the plant may not be detectable in its natural environment, but it is these compounds that will have the greatest potential for bioactivity. Endangered plants, because of their risk for extinction, have rarely been screened for bioactive compounds. Screening these novel plants will be the main focus of the company, but the same technology will provide protocols for the conservation and sustainable use of endangered plants. This I-Corps team has developed and optimized screening and isolation methods through its work with the Tennessee Center for Botanical Medicine Research to successfully test this proof-of-concept. The conventional approach of initially screening crude extracts could miss compounds active in trace amounts, such as signaling molecules, but methods being developed by this team will efficiently resolve extracts from different stressors into 5 to 10 compounds/sample. These samples will be initially screened in a 96-well format for activity in established anti-microbial, anti-cancer, and anti-inflammatory bioassays. Samples of interest will be further fractionated to pure compounds and rescreened to identify active compounds. This novel pipeline of drug leads will be very attractive for prospective partnerships and licensing with pharmaceutical companies while the team continues to develop high impact leads. Any lead that makes it to market will have an enormous impact on the lives of patients and their families.