Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives

Li, Xuqin; Wang, Lin; Liu, Yan; Hu, Tao; Zhang, Feilong; Cho, Chi-Hin; To, Kenneth K.W.

doi:10.1016/j.ejmech.2015.06.049

Cited by 52 publications

(25 citation statements)

References 31 publications

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“…A clear example of this is tariquidar, which initially was considered as a specific P-gp inhibitor, but later results showed inhibitory effects on BCRP and MRP1 leading to the synthesis of more potent tariquidar derivatives [106,107] . Mechanistic studies also showed that tariquidar can act, in a dosedependent manner, both as a substrate or as a transport inhibitor [106,108,109] .…”

Section: Inhibition Of P-gpmentioning

confidence: 99%

“…Furthermore, recent 3-dimensional quantitative structure-activity relationship (QSAR) studies of anthranilamide derivatives of tariquidar suggest that a hydrophobic domain is needed for increased P-gp specific inhibitory function [26] . Some tariquidar analogs with sulfonamide groups are P-gp specific, nevertheless tariquidar was toxic to healthy cells [107] . Since its discovery, tariquidar was described as non-competitive and non-transported inhibitor of P-gp [110] , while Bankstahl et al [111] have shown that tariquidar is concentration-dependently transported by P-gp.…”

Section: Inhibition Of P-gpmentioning

confidence: 99%

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How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

Jaramillo¹,

Saig²,

Cloos³

et al. 2018

CDR

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P-glycoprotein (ABCB1), multidrug resistance protein-1 (ABCC1) and breast cancer resistance protein (ABCG2) belong to the ATP-binding cassette (ABC) superfamily of proteins that play an important physiological role in protection of the body from toxic xenobiotics and endogenous metabolites. Beyond this, these transporters determine the toxicity profile of many drugs, and confer multidrug resistance (MDR) in cancer cells associated with a poor treatment outcome of cancer patients.It has long been hypothesized that inhibition of ABC drug efflux transporters will increase drug accumulation and thereby overcome MDR, but until now no approved inhibitor of these transporters is available in the clinic. In this review we present molecular strategies to overcome this type of drug resistance and discuss for each of these strategies their promising value or indicate underlying reasons for their limited success.

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Section: Inhibition Of P-gpmentioning

confidence: 99%

Section: Inhibition Of P-gpmentioning

confidence: 99%

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

Jaramillo¹,

Saig²,

Cloos³

et al. 2018

CDR

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“…Second- generation inhibitors such as valspodar and third generation such as tariquidar and zosuquidar are under clinical investigation ( Table 2 ). Unfortunately, many of the ABCB1 inhibitors may also inhibit cytochrome P450 and impair drug clearance, putting a risk of toxicity and adverse effects to normal cells (Pusztai et al, 2005; Kathawala et al, 2015; Li et al, 2015). …”

Section: The Atp-binding Cassette (Abc)mentioning

confidence: 99%

“…Another clinical trial on non-small cell lung cancer (NSCLC) patients, however, was suspended because it resulted in toxic effects and poor responses. Still, those contradicting results don’t change the fact that Tariquidar is a potent effective inhibitor and a lead compound with many analogs (Li et al, 2015). …”

Section: The Atp-binding Cassette (Abc)mentioning

confidence: 99%

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The Role of Eukaryotic and Prokaryotic ABC Transporter Family in Failure of Chemotherapy

Saleh²,

et al. 2017

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Over the years chemotherapy failure has been a vital research topic as researchers have been striving to discover reasons behind it. The extensive studies carried out on chemotherapeutic agents confirm that resistance to chemotherapy is a major reason for treatment failure. “Resistance to chemotherapy,” however, is a comprehensive phrase that refers to a variety of different mechanisms in which ATP-binding cassette (ABC) mediated efflux dominates. The ABC is one of the largest gene superfamily of transporters among both eukaryotes and prokaryotes; it represents a variety of genes that code for proteins, which perform countless functions, including drug efflux – a natural process that protects cells from foreign chemicals. Up to date, chemotherapy failure due to ABC drug efflux is an active research topic that continuously provides further evidence on multiple drug resistance (MDR), aiding scientists in tackling and overcoming this issue. This review focuses on drug resistance by ABC efflux transporters in human, viral, parasitic, fungal and bacterial cells and highlights the importance of the MDR permeability glycoprotein being the mutual ABC transporter among all studied organisms. Current developments and future directions to overcome this problem are also discussed.

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