The "specific" P-glycoprotein inhibitor Tariquidar is also a substrate and an inhibitor for breast cancer resistance protein (BCRP/ABCG2).

Abstract

Tariquidar was developed as a specific inhibitor of the efflux transporter ABCB1. Recent positron emission tomographic brain imaging studies using [(11)C]tariquidar to measure ABCB1 (P-gp, P-glycoprotein) density in mice indicate that the inhibitor may not be as specific as previously thought. We examined its selectivity as an inhibitor and a substrate for the human transporters P-gp, breast cancer resistance protein (BCRP, ABCG2), and multidrug resistance protein 1 (MRP1, ABCC1). Our results show that at low concentrations, tariquidar acts selectively as an inhibitor of P-gp and also as a substrate of BCRP. At much higher concentrations (≥100 nM), tariquidar acts as an inhibitor of both P-gp and BCRP. Thus, the in vivo specificity of tariquidar depends on concentration and the relative density and capacity of P-gp vs BCRP.

• Authors: Pavitra Kannan, Sanjay Telu, Suneet Shukla, Suresh V Ambudkar, Victor W Pike, Christer Halldin, Michael M Gottesman, Robert B Innis, Matthew D Hall
• Journal: ACS chemical neuroscience (ACS Chem Neurosci) Vol. 2 Issue 2 Pg. 82-9 (Feb 16 2011) ISSN: 1948-7193 [Electronic] United States
• PMID: 22778859 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ABCB1 protein, human
• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Neoplasm Proteins
• Quinolines
• tariquidar

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors, metabolism)
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (antagonists & inhibitors, metabolism)
• Breast Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Drug Resistance, Multiple (drug effects, physiology)
• Female
• HEK293 Cells
• Humans
• Neoplasm Proteins (antagonists & inhibitors, metabolism)
• Quinolines (chemistry, metabolism, pharmacology)
• Substrate Specificity (drug effects)