Updated chemical scaffolds of ABCG2 inhibitors and their structure-inhibition relationships for future development.

ATP-binding cassette (ABC) transporters are pivotal for cell detoxification and survival. Overexpression of ABC transporter in tumor cells lead to chemoresistance through the efflux of chemotherapeutic agents. P-glycoprotein (Pgp/ABCB1), multidrug resistance protein 1 (MRP1/ABCC1) and breast cancer resistance protein (BCRP/ABCG2) are the major ABC transporters involved in multidrug resistance (MDR) of cancer cells against anticancer drugs. ABCG2 is one of the major transporters involved in the efflux of different cytotoxic agents. Hence, inhibition of ABCG2-mediated transport is considered a prime target to resist MDR of cancer cells. Here, brief structural biology and functions of ABCG2 were discussed with the aim to identify key pharmacophoric elements to design potent and selective as well as non-toxic ABCG2 inhibitors. Structure-inhibition relationships (SIRs) of the earlier reported compounds were also explored. Taken together, this study offers insight for further development of ABCG2 inhibitors.