ZoBio, JH Oortweg 19, 2333CH, Leiden, Netherlands.
Gotham GmbH, Am Klopferspitz 19a, 82152, Martinsried, Germany.
J Biomol NMR. 2020 Nov;74(10-11):521-529. doi: 10.1007/s10858-020-00343-9. Epub 2020 Sep 8.
No matter the source of compounds, drug discovery campaigns focused directly on the target are entirely dependent on a consistent stream of reliable data that reports on how a putative ligand interacts with the protein of interest. The data will derive from many sources including enzyme assays and many types of biophysical binding assays such as TR-FRET, SPR, thermophoresis and many others. Each method has its strengths and weaknesses, but none is as information rich and broadly applicable as NMR. Here we provide a number of examples of the utility of NMR for enabling and providing ongoing support for the early pre-clinical phase of small molecule drug discovery efforts. The examples have been selected for their usefulness in a commercial setting, with full understanding of the need for speed, cost-effectiveness and ease of implementation.
无论化合物的来源如何，直接针对目标的药物发现活动都完全依赖于一致的可靠数据流，这些数据报告了假定配体与感兴趣的蛋白质如何相互作用。这些数据将来自许多来源，包括酶测定和许多类型的生物物理结合测定，如 TR-FRET、SPR、热泳和许多其他方法。每种方法都有其优点和缺点，但没有一种方法像 NMR 那样信息丰富且广泛适用。在这里，我们提供了一些 NMR 在小分子药物发现早期临床前阶段的应用实例，这些实例的选择是基于它们在商业环境中的实用性，同时充分了解速度、成本效益和易于实施的必要性。
