A New Practice: Study on the Molecular Mechanism of Traditional Chinese Medicine by Computational Pharmacology Methods: Part 1: Pharmacokinetic Modeling and Chemical Space Distribution

Ding-Hong      Wu; Xiao-Jie      Xu

Abstract

To study the drug-like features and ADME properties of Tongguan Capsule (TGC), a Traditional Chinese Medicine (TCM) for coronary heart disease (CHD). A systemic computational pharmacology approach about pharmacokinetic (PK) modeling was introduced to investigate the global nature of TGC, including chemical space distribution, prediction of ADME and construction of network. As a result, the natural components from TGC had similar chemical properties with synthetic drugs; prediction of ADME for TGC afforded an initial and plain view on the metabolism and safety through a macroscopic and holistic view, which involves complicated processes and mechanisms in vivo; the networks make the chemical similarity between natural components and synthetic drugs well visualized. Therefore, Computational approaches can promote our understanding on complex components and bioactivity, even the mechanism and metabolizing process in vivo of TGC.

Keywords: Computational pharmacology, Pharmacokinetic (PK) modeling, Tongguan capsule, Chemical space, ADME, Drug-drug network, Traditional Chinese Medicine (TCM), Pharmacodynamic (PD) Events, 3D-MSDT, QSAR, Cerius2, Discovery Studio, Chiral centers, Miklos Feher's, AloP98