C@PA: Computer-Aided Pattern Analysis to Predict Multitarget ABC Transporter Inhibitors

Based on literature reports of the last two decades, a computer-aided pattern analysis (C@PA) was implemented for the discovery of novel multitarget ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP) inhibitors. C@PA included basic scaffold identification, substructure search and statistical distribution, as well as novel scaffold extraction to screen a large virtual compound library. Over 45,000 putative and novel broad-spectrum ABC transporter inhibitors were identified, from which 23 were purchased for biological evaluation. Our investigations revealed five novel lead molecules as triple ABCB1, ABCC1, and ABCG2 inhibitors. C@PA is the very first successful computational approach for the discovery of promiscuous ABC transporter inhibitors.

Automated summary

This study utilized a computer-aided pattern analysis (C@PA) approach to discover novel multitarget ABC transporter inhibitors, successfully identifying over 45,000 potential inhibitors from a virtual compound library and revealing five novel lead molecules as triple ABCB1, ABCC1, and ABCG2 inhibitors. C@PA represents the first computational approach for the discovery of promiscuous ABC transporter inhibitors.