Faculty Opinions recommendation of The drug-target residence time model: a 10-year retrospective.

Author(s):  
John Lowe
2018 ◽  
Vol 18 (1) ◽  
pp. 84-84 ◽  
Author(s):  
Wilhelmus E. A. de Witte ◽  
Meindert Danhof ◽  
Piet H. van der Graaf ◽  
Elizabeth C. M. de Lange
Keyword(s):  

AIHAJ ◽  
1985 ◽  
Vol 46 (11) ◽  
pp. 679-689 ◽  
Author(s):  
MARK W. ACKLEY
Keyword(s):  

2019 ◽  
Vol 70 (1) ◽  
pp. 143-171 ◽  
Author(s):  
Mattia Bernetti ◽  
Matteo Masetti ◽  
Walter Rocchia ◽  
Andrea Cavalli

The kinetics of drug binding and unbinding is assuming an increasingly crucial role in the long, costly process of bringing a new medicine to patients. For example, the time a drug spends in contact with its biological target is known as residence time (the inverse of the kinetic constant of the drug-target unbinding, 1/ koff). Recent reports suggest that residence time could predict drug efficacy in vivo, perhaps even more effectively than conventional thermodynamic parameters (free energy, enthalpy, entropy). There are many experimental and computational methods for predicting drug-target residence time at an early stage of drug discovery programs. Here, we review and discuss the methodological approaches to estimating drug binding kinetics and residence time. We first introduce the theoretical background of drug binding kinetics from a physicochemical standpoint. We then analyze the recent literature in the field, starting from the experimental methodologies and applications thereof and moving to theoretical and computational approaches to the kinetics of drug binding and unbinding. We acknowledge the central role of molecular dynamics and related methods, which comprise a great number of the computational methods and applications reviewed here. However, we also consider kinetic Monte Carlo. We conclude with the outlook that drug (un)binding kinetics may soon become a go/no go step in the discovery and development of new medicines.


2016 ◽  
Vol 7 (9) ◽  
pp. 5945-5954 ◽  
Author(s):  
Fereidoon Daryaee ◽  
Andrew Chang ◽  
Johannes Schiebel ◽  
Yang Lu ◽  
Zhuo Zhang ◽  
...  

A mechanistic PK/PD model that enables predictions ofin vivodrug activity and an assessment of target vulnerability.


2014 ◽  
Vol 34 (4) ◽  
pp. 856-892 ◽  
Author(s):  
Dong Guo ◽  
Julia M. Hillger ◽  
Adriaan P. IJzerman ◽  
Laura H. Heitman

Sign in / Sign up

Export Citation Format

Share Document