Tariquidar

別名：XR9576

製品コード：S8028 純度：99.81%

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

CAS No. 206873-63-4

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 37000	国内在庫あり
10mg	JPY 25500	国内在庫あり
50mg	JPY 70500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（48）

製品安全説明書

現在のバッチを見る：純度： 99.81%

99.81

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シグナル伝達経路

P-gpシグナル伝達経路

P-gp阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
SW620	Cytotoxicity assay		48 hrs	Cytotoxicity against human SW620 cells assessed as cell viability after 48 hrs by MTT assay, IC50=25μM	26197160
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
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
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
K562/A02	Cytotoxicity assay		48 hrs	Cytotoxicity against human K562/A02 cells after 48 hrs by MTT assay, IC50=27.19μM	28645831
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
KBV1	Function assay		10 mins	Inhibition of ABCB1 in human KBV1 cells after 10 mins by Calcein-AM microplate assay, IC50=0.223μM	24900683
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
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
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
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
MDCK	Function assay			Inhibition of MDR1 expressed in MDCK cells using rhodamine 123 staining by flow cytometry, IC50=0.21μM	21354800
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
MCF7 MX	Function assay			Inhibition of BCRP expressed in MCF7 MX cells by Hoechst 33342 staining, IC50=0.68μM	19932960
MDCK	Function assay			Inhibition of BCRP expressed in MDCK cells by pheophorbide A assay, IC50=0.85μM	19932960
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
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
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
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
K562	Cytotoxicity assay		48 hrs	Cytotoxicity against human K562 cells after 48 hrs by MTT assay, IC50=31.56μM	28645831
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
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
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
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
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
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
HCT116	Cytotoxicity assay		48 hrs	Cytotoxicity against human HCT116 cells assessed as cell viability after 48 hrs by MTT assay, IC50=12.5μM	26197160
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
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
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/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
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生物活性

製品説明

Tariquidar is a potent and selective noncompetitive inhibitor of P-glycoprotein with K_d 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 B_max of 275 pmol/mg. Tariquidar shows non-competitive interaction with the P-gp substrates. Tariquidar increases the steady-state accumulation of these cytotoxics in CH^rB30 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)/ADR^RES multicellular tumor spheroid model derived from the MCF7^WT breast cancer cell line. ^[4]
Kinase Assay	Steady-state drug accumulation assay
Kinase 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.
細胞実験	細胞株	Murine mammary carcinoma cell line MDR EMT6/AR1.0
	濃度	~100 nM Tariquidar
	反応時間	4 days
	実験の流れ	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.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	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]
動物実験	動物モデル	Murine colon carcinoma xenografts MC26
	投与量	8 mg/kg
	投与経路	Coadministration of Tariquidar (p.o.) with doxorubicin (5 mg/kg, i.v.)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考
[1] Martin C, et al. Br J Pharmacol, 1999, 128(2), 403-411. [2] Robey RW, et al. Cancer Res, 2004, 64(4), 1242-1246. [3] Mistry P, et al. Cancer Res, 2001, 61(2), 749-758. [4] Walker J, et al. Eur J Cancer, 2004, 40(4), 594-605. + 展開

参考

[4] Walker J, et al. Eur J Cancer, 2004, 40(4), 594-605.

+ 展開

化学情報

分子量	646.73	化学式	C₃₈H₃₈N₄O₆
CAS No.	206873-63-4	SDF	Download Tariquidar SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 8 mg/mL ( (12.36 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

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Handling Instructions

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よくある質問（FAQ）

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

回答
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.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):