Understanding drug-target residence time and the implications on drug discovery

INTRODUCTION: High failure rates in clinical drug development are often attributed to inadequate therapeutic efficacy. While binding affinity has traditionally guided lead optimization, it reflects only the equilibrium state of drug-target interactions and often correlates poorly with in vivo pharmacological responses. This limitation has prompted growing interest in kinetic parameters that more accurately capture the dynamic nature of drug-target interactions. AREAS COVERED: ), which has emerged as a crucial determinant of drug efficacy. The authors discuss the impact of residence time on pharmacological outcomes, summarize factors influencing residence time, and outline experimental and computational…

• NN
  National Natural Science Foundation of China

  Awards: 22077110 and 22107090, 22377103
• NS
  Natural Science Foundation of Jiangsu Province

  Awards: BK20240051, BK20241043