Home Transmembrane Transporters P-gp inhibitor Tariquidar For research use only.

Tariquidar

Synonyms: XR9576

Tariquidar is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM in CHrB30 cell line, reverses drug resistance in MDR cell Lines. Phase 3.

Tariquidar Chemical Structure

Tariquidar Chemical Structure

CAS No. 206873-63-4

Purity & Quality Control

Tariquidar Related Products

Signaling Pathway

P-gp Signaling Pathways

P-gp Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
K562/DOX Function assay 1 uM 10 mins Inhibition of P-gp in human K562/DOX cells assessed as increase in rhodamine-123 efflux in human K562 cells at 1 uM incubated for 10 mins hrs by flow cytometry relative to untreated control 28113128
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
KB-V1 Function assay 200 nM Inhibition of P-gp in human KB-V1 cells assessed as increase in rhodamine 123 accumulation at 200 nM 21657271
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
HepG2 Cytotoxicity assay 48 hrs Cytotoxicity against adriamycin-resistant human HepG2 cells assessed as inhibition of cell proliferation after 48 hrs by MTT assay, IC50=37.2μM 27328029
K562 Cytotoxicity assay 48 hrs Cytotoxicity against human K562 cells after 48 hrs by MTT assay, IC50=31.56μM 28645831
K562 Cytotoxicity assay 48 hrs Cytotoxicity against human K562 cells assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=31.56μM 29631786
A2780adr Function assay 10 uM 30 mins Inhibition of ABCB1 in human A2780adr cells assessed as increase in accumulation of calcein AM at 10 uM preincubated for 30 mins followed by calcein AM addition measured every 60 secs for 60 mins by fluorescence assay relative to control 29547272
K562/A02 Cytotoxicity assay 48 hrs Cytotoxicity against human K562/A02 cells overexpressing P-gp assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=27.19μM 29631786
CCD-18Co Cytotoxicity assay 48 hrs Cytotoxicity against human CCD-18Co cells assessed as cell viability after 48 hrs by MTT assay, IC50=25μM 26197160
SW620/AD300 Cytotoxicity assay 48 hrs Cytotoxicity against human SW620/AD300 cells assessed as cell viability after 48 hrs by MTT assay, IC50=25μM 26197160
HLF Cytotoxicity assay 48 hrs Cytotoxicity against HLF cells assessed as inhibition of cell proliferation after 48 hrs by MTT assay, IC50=16.69μM 27328029
CEM/VLB500 Growth inhibition assay 3 days Growth inhibition of human CEM/VLB500 cells after 3 days by resazurin assay, GI50=13.5μM 17399990
MCF7/ADR Cytotoxicity assay 48 hrs Intrinsic cytotoxicity against human MCF7/ADR cells assessed as inhibition of cell proliferation after 48 hrs by MTT assay, IC50=13.1μM 27328029
HCT116 Cytotoxicity assay 48 hrs Cytotoxicity against human HCT116 cells assessed as cell viability after 48 hrs by MTT assay, IC50=12.5μM 26197160
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 treated for 48 hrs followed by compound washout measured after 12 hrs by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=8.28μM 28645831
KBV Function assay 5 uM 72 hrs Reversal of P-gp-mediated drug resistance in human KBV cells assessed as potentiation of cytotoxicity by measuring IC50 at 5 uM after 72 hrs by MTT assay (Rvb = 398.34 +/- 0.58 uM), IC50=5.24μM 30384042
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 treated for 48 hrs followed by compound washout measured after 6 hrs by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=4.97μM 28645831
KBV Function assay 10 uM 72 hrs Reversal of P-gp-mediated drug resistance in human KBV cells assessed as potentiation of cytotoxicity by measuring IC50 at 10 uM after 72 hrs by MTT assay (Rvb = 398.34 +/- 0.58 uM), IC50=4.46μM 30384042
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 treated for 48 hrs followed by compound washout measured immediately by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=3.02μM 28645831
K562/A02 Function assay 5 uM 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 at 5 uM measured after 48 hrs by MTT assay (Rvb = 43.75 to 96.91 uM), IC50=1.97μM 28645831
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 measured after 48 hrs by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=1.6μM 28645831
MCF-7 MX Function assay Inhibition of BCRP expressed in MCF-7 MX cells using Hoechst 33342 staining, IC50=1.5μM 21354800
MCF7 Function assay Inhibition of ABCG2 in human mitoxantrone-resistant MCF7 cells by Hoechst 33342 assay, IC50=1.44544μM 18678495
HFE Cytotoxicity assay 72 hrs Cytotoxicity against human HFE cells assessed as cell viability after 72 hrs by MTT assay, IC50=1.28μM 26197160
MDCK Function assay Inhibition of BCRP expressed in MDCK cells using Hoechst 33342 staining, IC50=0.94μM 21354800
MCF7/Topo Function assay Inhibition of ABCG2 overexpressed in human MCF7/Topo cells by flow cytometric-based mitoxantrone efflux assay, IC50=0.916μM 19170519
MCF7/Topo Function assay 2 hrs Inhibition of ABCG2 in human MCF7/Topo cells after 2 hrs by Hoechst 33342 staining based fluorescence assay, IC50=0.526μM 30128080
MCF7/Topo Function assay 2 hrs Inhibition of ABCG2 in human MCF7/Topo cells after 2 hrs by Hoechst 33342 microplate assay, IC50=0.526μM 24900683
MCF7/Topo Function assay Inhibition of ABCG2 expressed in human MCF7/Topo cells by Hoechst microplate assay, IC50=0.526μM 21570282
MCF7/Topo Function assay Inhibition of ABCG2 in human MCF7/Topo cells by Hoechst 33342 assay, IC50=0.52μM 26774038
KBV1 Function assay 10 mins Inhibition of ABCB1 in human KBV1 cells after 10 mins by Calcein-AM microplate assay, IC50=0.223μM 24900683
Kb-V1 Function assay 10 mins Inhibition of ABCB1 expressed in Kb-V1 cells after 10 mins by calcein-AM assay, IC50=0.223μM 21570282
KBv1 Function assay Inhibition of ABCB1 overexpressed in human KBv1 cells by flow cytometric-based calcein-AM efflux assay, IC50=0.223μM 19170519
KBV1 Function assay Inhibition of ABCB1 in human KBV1 cells assessed as inhibition of calcein-AM efflux, IC50=0.22μM 26774038
A2780 Function assay 30 mins Inhibition of human Pgp in A2780 cells after 30 mins by Hoechst 33342 assay, IC50=0.12589μM 18083034
KB-3-1 Function assay 1000 nM 72 hrs Potentiation of doxorubicin-induced cytotoxicity against human KB-3-1 cells assessed as doxorubicin IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 0.15 +/- 0.04 uM), IC50=0.11μM 27504669
OVCAR8 Function assay 1000 nM 72 hrs Potentiation of doxorubicin-induced cytotoxicity against human OVCAR8 cells assessed as doxorubicin IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 0.12 +/- 0.03 uM), IC50=0.08μM 27504669
A2780/ADR Function assay Inhibition of P-glycoprotein-mediated multidrug resistance in adriamycin-resistant human A2780/ADR cells by calcein AM assay, IC50=0.078μM 19250834
A2780adr Function assay Inhibition of P-gp expressed in A2780adr cells by calcein AM accumulation assay, IC50=0.08μM 21354800
A2780 Function assay Inhibition of P-gp in human adriamycin-resistant A2780 cells by Hoechst 33342 assay, IC50=0.07244μM 18678495
KBV1 Function assay 1000 nM 72 hrs Inhibition of human ABCB1 expressed in KBV1 cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 5.07 +/- 0.19 uM), IC50=0.07μM 27504669
CEM/VLB500 Function assay 3 days Reversal of P-gp-mediated multidrug resistance to in human CEM/VLB500 cells after 3 days by resazurin assay, EC50=0.068μM 17399990
EMT6/AR1.0 Function assay 1 hr Inhibition of mouse Pgp in EMT6/AR1.0 cells after 1 hr by daunorubicin accumulation assay, IC50=0.06457μM 18083034
EMT6/AR1.0 Function assay 1 hr Inhibition of mouse Pgp in EMT6/AR1.0 cells after 1 hr by daunorubicin accumulation assay, IC50=0.064μM 18083034
MDCK Function assay 30 mins Inhibition of P-glycoprotein (unknown origin) expressed in MDCK cells assessed as reduction of calcein-AM transport after 30 mins by fluorescence assay, EC50=0.044μM 24607999
MDCK Function assay 30 mins Activity at MDR1 (unknown origin) expressed in MDCK cells using calcein AM as substrate incubated for 30 mins prior to substrate addition measured after 30 mins by fluorometric analysis, EC50=0.044μM 23374872
NCI-ADR-RES Function assay 1000 nM 72 hrs Inhibition of human ABCB1 expressed in NCI-ADR-RES cells assessed as potentiation of cytotoxicity by measuring IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 3714.80 +/- 383.58 nM), IC50=0.01851μM 27504669
KBV1 Function assay 1000 nM 72 hrs Inhibition of human ABCB1 expressed in KBV1 cells assessed as potentiation of cytotoxicity by measuring IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 277.68 +/- 56.61 nM), IC50=0.00066μM 27504669
HEK293 Function assay 1000 nM 72 hrs Potentiation of doxorubicin-induced cytotoxicity against HEK293 cells assessed as doxorubicin IC50 at 1000 nM after 72 hrs by CCK8 assay (Rvb = 5.28 +/- 0.74 nM), IC50=0.00495μM 27504669
K562/A02 Cytotoxicity assay 48 hrs Cytotoxicity against human K562/A02 cells after 48 hrs by MTT assay, IC50=27.19μM 28645831
SW620 Cytotoxicity assay 48 hrs Cytotoxicity against human SW620 cells assessed as cell viability after 48 hrs by MTT assay, IC50=25μM 26197160
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 treated for 48 hrs followed by compound washout measured after 24 hrs by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=14.39μM 28645831
MDCK Function assay Inhibition of BCRP expressed in MDCK cells by pheophorbide A assay, IC50=0.85μM 19932960
MCF7 MX Function assay Inhibition of BCRP expressed in MCF7 MX cells by Hoechst 33342 staining, IC50=0.68μM 19932960
NCI-ADR-RES Function assay 1000 nM 72 hrs Inhibition of human ABCB1 expressed in NCI-ADR-RES cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 5.54 +/- 0.60 uM), IC50=0.24μM 27504669
MDCK Function assay Inhibition of MDR1 expressed in MDCK cells using rhodamine 123 staining by flow cytometry, IC50=0.21μM 21354800
CCRF-CEM/VCR1000 Function assay 240 secs Inhibition of P-glycoprotein-mediated daunorubicin efflux from human CCRF-CEM/VCR1000 cells after 240 secs by FACS flow cytometric analysis, IC50=0.03311μM 22452412
HEK293 Function assay 1000 nM 72 hrs Inhibition of human ABCB1 transfected in HEK293 cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 1000 nM after 72 hrs by CCK8 assay (Rvb = 504.65 +/- 44.94 nM), IC50=0.02477μM 27504669
KB-3-1 Function assay 1000 nM 72 hrs Potentiation of cytotoxicity against human KB-3-1 cells assessed as IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 0.78 +/- 0.27 nM), IC50=0.00041μM 27504669
OVCAR8 Function assay 1000 nM 72 hrs Potentiation of cytotoxicity against human OVCAR8 cells assessed as IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 8.53 +/- 1.95 nM), IC50=0.00518μM 27504669
MDCK Function assay 30 mins Activity at BCRP (unknown origin) expressed in MDCK cells using rhodamine 123 as substrate incubated for 30 mins prior to substrate addition measured after 30 mins by fluorometric analysis, EC50=0.01μM 23374872
HepG2 Function assay 10 uM 90 mins Inhibition of P-gp mediated efflux in adriamycin-resistant human HepG2 cells assessed as intracellular rhodamine-123 accumulation at 10 uM incubated in dark condition for 90 mins by flow cytometry relative to control 27328029
Click to View More Cell Line Experimental Data

Biological Activity

Description Tariquidar is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM in CHrB30 cell line, reverses drug resistance in MDR cell Lines. Phase 3.
Targets
P-gp [1]
(CHrB30 cells)
5.1 nM(Kd)
In vitro
In vitro

Tariquidar displays high-affinity binding to P-gp with Bmax of 275 pmol/mg. Tariquidar shows non-competitive interaction with the P-gp substrates. Tariquidar increases the steady-state accumulation of these cytotoxics in CHrB30 cells to levels observed in non-P-gp-expressing AuxB1 cells with EC50 of 487 nM. Tariquidar is able to inhibit the vanadate-sensitive ATPase activity of P-gp by 60-70%, with potent IC50 values of 43 nM. [1] Tariquidar may inhibit other resistance mechanisms at higher concentrations. 1 μM Tariquidar abrogates ABCG2 (BCRP)-mediated resistance to camptothecins in vitro. [2] Tariquidar potentiates the cyto-toxicity of several drugs including doxorubicin; complete reversal of resistance is achieved in the presence of 25- 80 nM Tariquidar. In MC26, a murine colon carcinoma cell line with intrinsic chemoresistance, the doxorubicin IC50 is fivefold lower in the presence of 0.1 μM Tariquidar (36 vs 7 nM). In murine mammary carcinoma, human small-cell lung carcinoma and human ovarian carcinoma cell lines with acquired chemotherapeutic resistance (EMT6/AR1.0, H69/LX4 and 2780 AD), the in vitro doxorubicin IC50 is 22-150-fold lower in the presence of 0.1 μM Tariquidar. P-gp inhibition persists for 23 h after removal of Tariquidar from the culture system. [3] Tariquidar restored the cyto-toxicity of doxorubicin in the National Cancer Institute (NCI)/ADRRES multicellular tumor spheroid model derived from the MCF7WT breast cancer cell line. [4]
Kinase Assay Steady-state drug accumulation assay
Cells are incubated in a reaction volume of 1 mL for 60 min at 37 ℃ under 5% CO2 in order to reach steady-state. The effect of the modulators XR9576 on [3H]-ligand accumulation is investigated in the concentration range 10-9 - 10-6 M. Modulators are added from a DMSO stock giving a final solvent concentration of 0.2 % (v/v). Following cell harvesting, accumulated drug is measured by liquid scintillation counting and normalized for cell protein content. Plots of amount accumulated as a function of modulator concentration are fitted with the general dose-response equation: Y={(a-b)/(1+(X/c)d)}+bWhere: Y=response; a=initial response; b=final response; c=EC50 concentration; d=slope value; X=drug concentration.
Cell Research Cell lines Murine mammary carcinoma cell line MDR EMT6/AR1.0
Concentrations ~100 nM Tariquidar
Incubation Time 4 days
Method

Cells are seeded into 96-well plates at 800/well, in 100 μL of medium and incubated for 4 h at 37 ℃. Varying concentrations of modulator or solvent control (50 μL/well) are subsequently added and incubated for an additional 1 h before the addition of the cytotoxic drug. The cytotoxic drug (50 μL) is added to give a range of final concentrations in quadruplicate wells. After incubation for an additional 4 days, cell proliferation of adherent cells is assessed using the sulforhodamine B assay.
Experimental Result Images Methods Biomarkers Images PMID
Immunofluorescence MRP7 23393594
In Vivo
In vivo

Tariquidar (2- 8 mg/kg p.o.) is found to significantly potentiate the antitumor activity of doxorubicin (5 mg/kg, i.v.) against MC26 murine colon carcinoma in vivo. In human carcinoma xenografts, coadministration of XR9576 (6 -12 mg/kg p.o.) fully restored the antitumor activity against two highly resistant MDR human tumor xenografts (2780AD, H69/LX4) in nude mice. [3]
Animal Research Animal Models Murine colon carcinoma xenografts MC26
Dosages 8 mg/kg
Administration Coadministration of Tariquidar (p.o.) with doxorubicin (5 mg/kg, i.v.)
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01663545 Completed
Epilepsies Partial
National Institute of Neurological Disorders and Stroke (NINDS)|National Institutes of Health Clinical Center (CC)
 July 31 2012 --
NCT01547754 Terminated
HIV-Associated Cognitive Motor Complex
National Institute of Mental Health (NIMH)|National Institutes of Health Clinical Center (CC)
 January 9 2012 --
NCT01386476 Completed
Drug Resistance
National Institute of Mental Health (NIMH)|National Institutes of Health Clinical Center (CC)
 June 15 2011 --
NCT00082368 Completed
Cancer
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 May 16 2004 Phase 2

Chemical Information & Solubility

Molecular Weight 646.73 Formula

C38H38N4O6
CAS No. 206873-63-4 SDF Download Tariquidar SDF
Smiles COC1=C(C=C2CN(CCC2=C1)CCC3=CC=C(C=C3)NC(=O)C4=CC(=C(C=C4NC(=O)C5=CC6=CC=CC=C6N=C5)OC)OC)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 8 mg/mL ( (12.36 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
Can you please give me more specific and detailed information of how to dissolve and use this compound (S8028) for in vivo studies?

Answer:
Tariquidar in 30% Propylene glycol, 5% Tween 80, 65% D5W at 30mg/ml will be a suspension or emulsion. If you are going to administrate the compound by oral gavage, it is fine. We also have test some vehicles for Tariquidar for i.p injection, and it is soluble in 5% DMSO+45% PEG 300+ddH2O at 2mg/ml clearly. When preparing the solution, please dissolve the compound in DMSO clearly first, then add PEG. After they mixed well, then dilute with water.

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