Schuetz Doris A, de Witte Wilhelmus Egbertus Arnout, Wong Yin Cheong, Knasmueller Bernhard, Richter Lars, Kokh Daria B, Sadiq S Kashif, Bosma Reggie, Nederpelt Indira, Heitman Laura H, Segala Elena, Amaral Marta, Guo Dong, Andres Dorothee, Georgi Victoria, Stoddart Leigh A, Hill Steve, Cooke Robert M, De Graaf Chris, Leurs Rob, Frech Matthias, Wade Rebecca C, de Lange Elizabeth Cunera Maria, IJzerman Adriaan P, Müller-Fahrnow Anke, Ecker Gerhard F
Department of Pharmaceutical Chemistry, University of Vienna, UZA 2, Althanstrasse 14, 1090 Vienna, Austria.
Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Drug Discov Today. 2017 Jun;22(6):896-911. doi: 10.1016/j.drudis.2017.02.002. Epub 2017 Apr 13.
A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target-ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further. In this review, we highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium, which targets major open questions related to binding kinetics in an industry-driven public-private partnership.
相当数量的已批准药物表现出非平衡结合特性，这凸显了药物驻留时间对体内疗效的潜在作用。因此，详细了解靶标-配体复合物的结合和解离动力学可能会为化合物的分子作用机制提供关键见解。这种更深入的理解将有助于改善药物研发中的决策，从而更好地选择值得进一步研究的有趣化合物。在本综述中，我们重点介绍了药物发现动力学（K4DD）联盟所做的贡献，该联盟在行业驱动的公私合作关系中致力于解决与结合动力学相关的主要开放性问题。
