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

Eur J Med Chem. 2022 Nov 5:241:114628. doi: 10.1016/j.ejmech.2022.114628. Epub 2022 Jul 31.

Abstract

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.

Keywords: ABCG2; ABCG2 inhbitor; MDR; Medicinal chemistry; SIRs.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • ATP-Binding Cassette Transporters / metabolism
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Neoplasm Proteins* / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Neoplasm Proteins