Systems Pharmacology in Small Molecular Drug Discovery

Int J Mol Sci. 2016 Feb 18;17(2):246. doi: 10.3390/ijms17020246.


Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

Keywords: ADME/T; drug discovery; network pharmacology; systems pharmacology.

Publication types

  • Review

MeSH terms

  • Computational Biology / methods
  • Computer Simulation
  • Drug Design
  • Drug Discovery* / methods
  • Humans
  • Ligands
  • Molecular Targeted Therapy
  • Neural Networks, Computer
  • Pharmacology* / methods
  • Phenotype
  • Quantitative Structure-Activity Relationship
  • Small Molecule Libraries*
  • Systems Biology* / methods


  • Ligands
  • Small Molecule Libraries