HobPre: accurate prediction of human oral bioavailability for small molecules

J Cheminform. 2022 Jan 6;14(1):1. doi: 10.1186/s13321-021-00580-6.

Authors

Min Wei¹, Xudong Zhang¹, Xiaolin Pan¹, Bo Wang¹, Changge Ji^{1

2}, Yifei Qi³, John Z H Zhang^{4

5

6

7

8}

Affiliations

¹ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
² NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, 200062, China.
³ Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China. yfqi@fudan.edu.cn.
⁴ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China. John.zhang@nyu.edu.
⁵ NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, 200062, China. John.zhang@nyu.edu.
⁶ Department of Chemistry, New York University, New York, NY, 10003, USA. John.zhang@nyu.edu.
⁷ Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China. John.zhang@nyu.edu.
⁸ Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, Shanxi, 030006, China. John.zhang@nyu.edu.

Abstract

Human oral bioavailability (HOB) is a key factor in determining the fate of new drugs in clinical trials. HOB is conventionally measured using expensive and time-consuming experimental tests. The use of computational models to evaluate HOB before the synthesis of new drugs will be beneficial to the drug development process. In this study, a total of 1588 drug molecules with HOB data were collected from the literature for the development of a classifying model that uses the consensus predictions of five random forest models. The consensus model shows excellent prediction accuracies on two independent test sets with two cutoffs of 20% and 50% for classification of molecules. The analysis of the importance of the input variables allowed the identification of the main molecular descriptors that affect the HOB class value. The model is available as a web server at www.icdrug.com/ICDrug/ADMET for quick assessment of oral bioavailability for small molecules. The results from this study provide an accurate and easy-to-use tool for screening of drug candidates based on HOB, which may be used to reduce the risk of failure in late stage of drug development.

Keywords: ADMET; Classification; Molecular descriptors; Oral bioavailability; Prediction.

Abstract

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