AP 4. Drug Screening and Pharmacology

摘要：AP4 PMS-ICBG的这项联合计划将测试AP3中确定的天然产品的药用 在治疗几种重要疾病方面具有潜力。我们选择我们的疾病目标是考虑到：1)未实现 人类健康需求；2)菲律宾的健康需求；3)与我们的生态理念密切相关的分析 和AP2的共生研究；4)提供创新和保守药物治疗方法的混合 发现号。我们的检测针对涉及神经元受体、离子通道和其他蛋白质的条件； 胰腺癌；胶质母细胞瘤；耐药的“ESKAPE”感染；以及顶端复合体寄生虫 感染，重点是隐孢子虫和弓形虫。此外，我们还与 适当的实体，有进一步的分析可用，并且非常适合帮助我们将发现转化为 转化为对人类健康有积极影响的产品。 美联社的一个特别创新的焦点是我们使用了最近发明的“星座药理学”。 方法，提供了一种针对自然分化的哺乳动物细胞进行高含量筛选的方法 类型。初步数据表明，这种方法在寻找极具挑战性的靶标方面非常有前景， 在这里，我们将通过筛选天然产品进一步做到这一点。提出了这一方法和其他创新方法 以久经考验的药物发现方法加强，以提供相对全面的筛查 我们的图书馆。 最后，我们开发了一些策略来验证HITS并在早期确定它们的翻译潜力 学习。作为这一计划的一部分，有前途的候选人将得到进一步的调查。 为达致这些目标，我们计划： 1)从AP3中提取的筛选优先片段； 2)将星座筛选用于神经科和癌症药物的发现； 3)采用新的抗生素发现方法； 4)采用新的抗寄生虫检测方法； 5)确定分子靶点，进一步开发化合物。

Summary: AP4 This associate program of PMS-ICBG will test natural products identified in AP3 for their pharmaceutical potential in treating several important diseases. We have selected our disease targets by considering:1) unmet needs in human health; 2) health needs in the Philippines; 3) assays that have a strong tie to our eco-rationale and symbiosis studies in AP2; 4) that provide a mix of innovative and conservative approaches to drug discovery. Our assays target conditions that involve neuronal receptors, ion channels, and other proteins; pancreatic cancer; glioblastoma; pandrug-resistant "ESKAPE" infections; and apicomplexan parasite infections, with a focus on Crytosporidium and Toxoplasma. Further, we have formed interactions with appropriate entities that have further assays available and that are well suited to help us translate discoveries into products that will have a positive impact on human health. A particularly innovative focus of this AP is our use of the recently invented "constellation pharmacology" method, which provides a method for high-content screening against naturally differentiated mammalian cell types. Preliminary data show that this method is very promising in finding ligands for very challenging targets, and here we will take that further by screening natural products. This and other innovative methods proposed are reinforced with time-tested approaches to drug discovery to provide a relatively comprehensive screening of our library. Finally, we have developed strategies to validate hits and to determine their translational potential early on in studies. Promising candidates will be further investigated as part of this program. To achieve these goals, we plan to: 1) Screen priority extracts from AP3; 2) Employ constellation screening for neurological and cancer drug discovery; 3) Employ novel assays for antibiotic discovery; 4) Employ novel assays against parasites; 5) Identify molecular targets and further develop compounds.