SUMMARY: P-glycoprotein (P-gp) is a member of ABC transporter family that actively pumps xenobiotics out of cells to protect organisms from toxic compounds. P-gp substrates can be easily pumped out of the cells to reduce their absorption; conversely P-gp inhibitors can reduce such pumping activity. Hence, it is crucial to know if a drug is a P-gp substrate or inhibitor in view of pharmacokinetics. Here we present PgpRules, an online P-gp substrate and P-gp inhibitor prediction server with ruled-sets. The two models were built using classification and regression tree algorithm. For each compound uploaded, PgpRules not only predicts whether the compound is a P-gp substrate or a P-gp inhibitor, but also provides the rules containing chemical structural features for further structural optimization. AVAILABILITY AND IMPLEMENTATION: PgpRules is freely accessible at https://pgprules.cmdm.tw/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Bioinformatics (2019) doi: 10.1093/bioinformatics/btz213 In the above article the following funding statement was inadvertently omitted: ‘This work was supported by the NTU SPARK program, Ministry of Science and Technology, Taiwan (most 107-2823-8-002-003-), and Computational Molecular Design and Metabolomics Laboratory, Department of Computer Science and Information Engineering at National Taiwan University.’ This has now been corrected. The author apologises for the error.

UNLABELLED: Cytochrome P450 (CYPs) are the major enzymes involved in drug metabolism and bioactivation. Inhibition models were constructed for five of the most popular enzymes from the CYP superfamily in human liver. The five enzymes chosen for this study, namely CYP1A2, CYP2D6, CYP2C19, CYP2C9 and CYP3A4, account for 90% of the xenobiotic and drug metabolism in human body. CYP enzymes can be inhibited or induced by various drugs or chemical compounds. In this work, a rule-based CYP inhibition prediction online server, CypRules, was created based on predictive models generated by the rule-based C5.0 algorithm. CypRules can predict and provide structural rulesets for CYP inhibition for each compound uploaded to the server. Capable of fast execution performance, it can be used for virtual high-throughput screening (VHTS) of a large set of testing compounds. AVAILABILITY AND IMPLEMENTATION: CypRules is freely accessible at http://cyprules.cmdm.tw/ and models, descriptor and program files for all compounds are publically available at http://cyprules.cmdm.tw/sources/sources.rar.