In silico ADME/T modelling for rational drug design.
In recent decades, in silico absorption, distribution, metabolism, excretion (ADME), and toxicity (T) modelling as a tool for rational drug design has received considerable attention from pharmaceutical scientists, and various ADME/T-related prediction models have been reported. The high-throughput and low-cost nature of these models permits a more streamlined drug development process in which the identification of hits or their structural optimization can be guided based on a parallel investigation of bioavailability and safety, along with activity. However, the effectiveness of these tools is highly dependent on their capacity to cope with needs at different stages, e.g. their use in candidate selection has been limited due to their lack of the required predictability. For some events or endpoints involving more complex mechanisms, the current in silico approaches still need further improvement. In this review, we will briefly introduce the development of in silico models for some physicochemical parameters, ADME properties and toxicity evaluation, with an emphasis on the modelling approaches thereof, their application in drug discovery, and the potential merits or deficiencies of these models. Finally, the outlook for future ADME/T modelling based on big data analysis and systems sciences will be discussed.
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Yulan
Y
Wang
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Jing
J
Xing
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Yuan
Y
Xu
State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of Chemical Biology,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China.
Nannan
N
Zhou
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Jianlong
J
Peng
School of Life Science and Technology,Shanghai Tech University,Shanghai 200031,China.
Zhaoping
Z
Xiong
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Xian
X
Liu
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Xiaomin
X
Luo
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Cheng
C
Luo
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Kaixian
K
Chen
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Mingyue
M
Zheng
Drug Discovery and Design Center, State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China.
Hualiang
H
Jiang
D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D001692:Biological Transport; D001812:Blood-Brain Barrier; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D007422:Intestines / Q000473:pathology; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D008968:Molecular Conformation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D013816:Thermodynamics
D008024:Ligands
ADME/T; Drug Design; Pharmacokinetics; Predictive Toxicology; QSAR