网络药理学学习记录8：预测药物的ADME性质

SwissADME
http://www.swissadme.ch/

SwissADME网站可以计算一个或多个小分子的理化指标，并预测ADME参数，药代动力学特性，类药物性质和药物化学友好性，以支持药物发现。这是一个免费的Web工具，用于评估小分子的药代动力学，药物相似性和药物化学友好性。这是由瑞士生物信息学研究所分子建模小组开发和维护。ADME是Absorption, distribution, metabolism, excretion and toxicity (ADMET) 的缩写。

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• 结果生成

  
  

Swissadme结果分析范例：
（1）

Lipinski’s rule of 5 was used to predict the drug-likeness of our hits from the ZINC15 library. Lipinski’s rule of 5 states that for any ligand to be considered as a drug-like, a molecule should obey these criteria: molecular weight <500 Dalton, number of H-bond donors <5, number of H-bond acceptors <10 and LogP <5 (Lipinski, 2004). Accordingly, all of our hits obeyed this rule and thus considered as drug-like compounds. Furthermore, our compounds were found to be within the reference range considering their water solubility (LogS), Caco-2 permeability and topological polar surface area (TPSA) (Table 4).

（2）

Ligands with high solubility and bioavailability were further taken for the interaction analysis.

（3）

The drug likeliness of a molecule is indicated by the Lipinski’s rule of five parameters (molecular weight <500 Da, no more than 5 hydrogen bond donors, no. of hydrogen bond acceptors should be less than 10 and logP should not be greater than 5). The Lipinski’s rule of five parameters were obtained from the SWISSADME server (www.swissadme.ch/index.php) (Daina et al., 2017). The chemical structures, chemical formula and the Lipinski’s rule parameters of the ligands are listed in Table S1 (Supplementry Information).

(4)

Since in silico ADMET prediction can help early drug design and evaluation, ADMET properties of the 67 key compounds were predicted by SwissADME and pkCSM. Chemical properties including molecular weight (MW), rotatable bonds count, H-bond acceptors and donors count, TPSA and leadlikeness violations were calculated by SwissADME and shown as Fig. 8A. It is worth mentioning that 21 (31.34 %) compounds passed the stringent lead-like criteria (250 g/mol ≤ MW ≤ 350 g/mol, XLOGP ≤ 3.5 and rotatable bonds ≤ 7), which are excellent candidates for drug discovery (Fig. 7A). And these lead-likeness compounds were further predicted by pkCSM, with the exception of S3 (low gastrointestinal absorption)