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Effect of OATP-binding on the prediction of biliary excretion

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posted on 2023-06-09, 03:25 authored by Mohsen Sharifi, Taravat Ghafourian
1.Biliary excretion of compounds is dependant on several transporter proteins for the active uptake of compounds from the blood into the hepatocytes. Organic anion-transporting polypeptides (OATPs) are some of the most abundant transporter proteins in the sinusoidal membrane and have been shown to have substrate specificity similar to the structural characteristics of cholephilic compounds. 2.In this study, we sought to use measures of OATP binding as predictors of biliary excretion in conjunction with molecular descriptors in a quantitative structure-activity relationship (QSAR) study. Percentage inhibitions of three subtypes of OATPs were used as surrogate indicators of OATP substrates. Several statistical modelling techniques were incorporated including classification and regression trees, boosted trees, random forest and multivariate adaptive regression splines (MARS) in order to first develop QSARs for the prediction of OATP inhibition of compounds. The predicted OATP percentage inhibition using selected models were then used as features of the QSAR models for the prediction of biliary excretion of compounds in rat. 3.The results indicated that incorporation of predicted OATP inhibition improves accuracy of biliary excretion models. The best result was obtained from a simple regression tree that used predicted OATP1B1 percentage inhibition at the root node of the tree.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Xenobiotica

ISSN

0049-8254

Publisher

Taylor & Francis

Issue

7

Volume

47

Page range

614-631

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-10-11

First Open Access (FOA) Date

2017-08-03

First Compliant Deposit (FCD) Date

2016-10-11

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