Given the therapeutic and commercial success of small-molecule enzyme inhibitors, as exemplified by kinase inhibitors in oncology, a major focus of current drug-discovery and development efforts is on enzyme targets. Understanding the course of an enzyme-catalysed reaction can help to conceptualize different types of inhibitor and to inform the design of screens to identify desired mechanisms. Exploiting this information allows the thorough evaluation of diverse compounds, providing the knowledge required to efficiently optimize leads towards differentiated candidate drugs. This review highlights the rationale for conducting high-quality mechanistic enzymology studies and considers the added value in combining such studies with orthogonal biophysical methods.

鉴于小分子酶抑制剂的治疗和商业成功（如肿瘤学中激酶抑制剂的例子），当前药物发现和开发工作的主要重点是酶靶标。了解酶催化反应的过程可以帮助概念化不同类型的抑制剂，并有助于筛选设计以鉴定所需的机制。利用这些信息可以对各种化合物进行全面评估，从而提供有效优化导致差异化候选药物所需的知识。这篇综述强调了进行高质量机械酶学研究的基本原理，并考虑了将此类研究与正交生物物理方法相结合的附加价值。