Purpose: Although the ABCB1 (P-glycoprotein) drug transporter is a constituent of several blood–tissue barriers (i.e., blood–brain and blood–nerve), its participation in a putative blood–heart barrier has been poorly explored. ABCB1 could decrease the intracardiac concentrations of drugs that cause QT prolongation and cardiotoxicity. Experimental Design: ABCB1-related romidepsin transport kinet...

Multidrug resistance (MDR), mainly mediated by ABCB1 transporter, is a major cause for chemotherapy failure. Bufalin (BU), an active component of the traditional Chinese medicine chan'su, has been reported to have antitumor effects on various types of cancer cells. The purpose of this present study was to investigate the reversal effect of BU on ABCB1-mediated multidrug resistance in colorectal...

PURPOSE The clinically approved oncogenic BRAF inhibitor PLX4032 (vemurafenib) was shown to be a substrate of the ATP-binding cassette (ABC) transporter ABCB1. Here, we compared PLX4032 and its structurally closely related precursor compound PLX4720 for their interference with ABCB1 and the ABCB1-mediated compound transport using docking and cell culture experiments. METHODS For the docking s...

The overexpression of ATP-binding cassette (ABC) transporters often leads to the development of multidrug resistance (MDR), which is the major factor contributing to the failure of chemotherapy. The objective of this study was to investigate the enhancement of CEP-33779, a small-molecule inhibitor of Janus kinase 2 (JAK2), on the efficacy of conventional chemotherapeutic agents in MDR cells wit...

Cyclin-dependent kinase inhibitors (CDKi) have high potential applicability in anticancer therapy, but various aspects of their pharmacokinetics, especially their interactions with drug efflux transporters, have not yet been evaluated in detail. Thus, we investigated interactions of five CDKi (purvalanol A, olomoucine II, roscovitine, flavopiridol and SNS-032) with the ABCB1 transporter. Four o...

PURPOSE Previous studies show that inhibition of ABCB1 expression overcomes acquired docetaxel resistance in C4-2B-TaxR cells. In this study, we examined whether antiandrogens, such as bicalutamide and enzalutamide, could inhibit ABCB1 activity and overcome resistance to docetaxel. EXPERIMENTAL DESIGN ABCB1 efflux activity was determined using a rhodamine efflux assay. ABCB1 ATPase activity w...

ABCB1 and ABCG2 work together at the blood-brain barrier (BBB) to limit brain distribution of dual ABCB1/ABCG2 substrates. In this pilot study we used positron emission tomography (PET) to assess brain distribution of two model ABCB1/ABCG2 substrates ([(11) C]elacridar and [(11) C]tariquidar) in healthy subjects without (c.421CC) or with (c.421CA) the ABCG2 single-nucleotide polymorphism (SNP) ...

Single-nucleotide polymorphisms (SNPs) in the gene coding for the efflux-transport protein ABCB1 (P-glycoprotein) are commonly inherited as haplotypes. ABCB1 SNPs and haplotypes have been suggested to influence the pharmacokinetics and therapeutic outcome of the tyrosine kinase inhibitor (TKI) imatinib, used for treatment of chronic myeloid leukemia (CML). However, no consensus has yet been rea...

PURPOSE Although the ABCB1 (P-glycoprotein) drug transporter is a constituent of several blood-tissue barriers (i.e., blood-brain and blood-nerve), its participation in a putative blood-heart barrier has been poorly explored. ABCB1 could decrease the intracardiac concentrations of drugs that cause QT prolongation and cardiotoxicity. EXPERIMENTAL DESIGN ABCB1-related romidepsin transport kinet...

Chemotherapy is one of the most common therapeutic option for metastatic tumors and hematological malignancies. ABCB1-mediated multidrug resistance is the major obstacle for chemotherapy. Natural products with diversified structures are ideal source of ABCB1 modulators. Ganoderenic acid B, a lanostane-type triterpene isolated from Ganoderma lucidum, exhibited potent reversal effect on ABCB1-med...