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Tariquidar

別名: XR9576

Tariquidar是一種有效的，選擇性的，非競(jìng)爭(zhēng)性P-glycoprotein抑制劑，在CHrB30細(xì)胞系中Kd為5.1 nM，作用于MDR細(xì)胞系逆轉(zhuǎn)耐藥性。Phase 3。

Tariquidar Chemical Structure

Tariquidar Chemical Structure

CAS: 206873-63-4

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買(mǎi)數(shù)量
10mM (1mL in DMSO) 1970 現(xiàn)貨
10mg 1415.55 現(xiàn)貨
50mg 3846.69 現(xiàn)貨
1g 24488.1 現(xiàn)貨
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400-668-6834

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Tariquidar相關(guān)產(chǎn)品

相關(guān)信號(hào)通路圖

P-gp Signaling Pathways

P-gp信號(hào)通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類(lèi)型 給藥濃度 孵育時(shí)間 活性描述 文獻(xiàn)信息
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

產(chǎn)品描述 Tariquidar是一種有效的，選擇性的，非競(jìng)爭(zhēng)性P-glycoprotein抑制劑，在CHrB30細(xì)胞系中Kd為5.1 nM，作用于MDR細(xì)胞系逆轉(zhuǎn)耐藥性。Phase 3。
靶點(diǎn)
P-gp [1]
(CHrB30 cells)
5.1 nM(Kd)
體外研究(In Vitro)
體外研究活性

Tariquidar高親和力結(jié)合到P-gp，Bmax為275 pmol/mg。Tariquidar與P-gp底物非競(jìng)爭(zhēng)性地相互作用。Tariquidar作用于CHrB30 細(xì)胞，增加這些細(xì)胞毒素的穩(wěn)態(tài)積累，達(dá)到非P-gp表達(dá)的AuxB1細(xì)胞中觀(guān)察的水平，EC50為487 nM。Tariquidar可以抑制 P-gp的對(duì)Vanadate敏感的ATPase活性，抑制達(dá) 60-70%,有效IC50值為43 nM。[1]Tariquidar高濃度時(shí)，可以抑制其他耐藥機(jī)制。1 μM Tariquidar在體外，可以廢除ABCG2（BCRP）介導(dǎo)的Camptothecins耐藥性。[2]Tariquidar增強(qiáng)幾種藥物的細(xì)胞毒性，包括Doxorubicin。處理具有內(nèi)在耐藥性的小鼠結(jié)腸癌細(xì)胞系MC26，Doxorubicin比0.1 μM Tariquidar (36 vs 7 nM)的IC50值低5倍。處理具有獲得性化療抗性的小鼠乳腺癌，人類(lèi)小細(xì)胞肺癌，和和人類(lèi)卵巢癌細(xì)胞系(EMT6/AR1.0, H69/LX4 和 2780 AD)，Doxorubicin 比0.1 μM Tariquidar的IC50值低22-150倍。從培養(yǎng)系統(tǒng)除去Tariquidar后，P-gp的抑制作用持續(xù)23小時(shí)。[3]Tariquidar恢復(fù)Doxorubicin作用于MCF7WT乳腺癌細(xì)胞系衍生的多細(xì)胞腫瘤球體模型的細(xì)胞毒性。[4]
激酶實(shí)驗(yàn) 穩(wěn)態(tài)藥物累積實(shí)驗(yàn)
細(xì)胞在37°C下5% CO2環(huán)境中溫育60分鐘，達(dá)到穩(wěn)態(tài)，反應(yīng)體積為1 mL。在10-9-10-6 M濃度范圍內(nèi) 調(diào)查調(diào)節(jié)劑XR9576對(duì)[3H]-配體累積的影響。DMSO儲(chǔ)存液中加入調(diào)節(jié)劑，最終溶劑濃度為0.2 %(v/v)。細(xì)胞收集后，通過(guò)液體閃爍計(jì)數(shù)和歸一化細(xì)胞蛋白質(zhì)含量測(cè)量累計(jì)的藥物。
細(xì)胞實(shí)驗(yàn) 細(xì)胞系 小鼠乳腺癌細(xì)胞系MDR EMT6/AR1.0
濃度 ~100 nM Tariquidar
孵育時(shí)間 4 天
方法

細(xì)胞按每孔800個(gè)接種在含100 μL 培養(yǎng)基的96孔板中，在37°C下溫育4小時(shí)。隨后加入不同濃度的調(diào)節(jié)劑或溶劑對(duì)照（50μL/孔），再溫育1小時(shí)，加入細(xì)胞毒性藥物。加入細(xì)胞毒性藥物（50μL），每孔按一式四份得到終濃度的范圍。再溫育4天 ,通過(guò)Sulforhodamine B實(shí)驗(yàn)測(cè)評(píng)貼壁細(xì)胞的細(xì)胞增殖。
實(shí)驗(yàn)圖片 檢測(cè)方法 檢測(cè)指標(biāo) 實(shí)驗(yàn)圖片 PMID
Immunofluorescence MRP7 23393594
體內(nèi)研究(In Vivo)
體內(nèi)研究活性

Tariquidar(2-8 mg/kg 口服處理)顯著增強(qiáng)Doxorubicin(5 mg/kg, 靜脈注射)處理MC26小鼠結(jié)腸癌的抗腫瘤活性。Tariquidar和XR9576(6-12 mg/kg 口服處理)合用共處理人類(lèi)移植瘤， 完全恢復(fù)作用于兩個(gè)高度抗MDR的人類(lèi)移植瘤(2780AD, H69/LX4)的抗腫瘤活性。[3]
動(dòng)物實(shí)驗(yàn) Animal Models 攜帶結(jié)腸癌移植瘤MC26的小鼠
Dosages 8 mg/kg
Administration Tariquidar (口服處理)和Doxorubicin (5 mg/kg,靜脈注射）共處理
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

化學(xué)信息&溶解度

分子量 646.73 分子式

C38H38N4O6
CAS號(hào) 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
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

DMSO : 8 mg/mL ( (12.36 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

 動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量 濃度 體積 分子量

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

mg/kg g μL 只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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常見(jiàn)問(wèn)題及建議解決方法

問(wèn)題 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.

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