Tariquidar

製品コードS8028 バッチS802803

印刷

化学情報

Chemical Structure Synonyms XR9576 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C38H38N4O6
分子量 646.73 CAS No. 206873-63-4
Solubility (25°C)* 体外 DMSO 5.6 mg/mL (8.65 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO Corn oil
0.28mg/ml Taking the 1 mL working solution as an example, add 50 μL of 5.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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 vinblastine and paclitaxel. 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, paclitaxel, etoposide, and vincristine; 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 and vinblastine in the National Cancer Institute (NCI)/ADRRES multicellular tumor spheroid model derived from the MCF7WT breast cancer cell line. [4]
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 of paclitaxel, etoposide, and vincristine against two highly resistant MDR human tumor xenografts (2780AD, H69/LX4) in nude mice. [3]

プロトコル(参考用のみ)

キナーゼアッセイ Steady-state drug accumulation assay
AuxB1 and CHrB30 cells are grown to confluency in 12-well (24 mm) tissue culture dishes and the steady-state accumulation of [3H]-vinblastine is measured. Accumulation is initiated by the addition of 0.1 μ Ci [3H]-vinblastine and unlabelled vinblastine to a final concentration of 100 nM . The accumulation of [3H]-paclitaxel is measured using 0.1 μ Ci [3H]-paclitaxel and unlabelled drug to a final concentration of 1 μM . 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.
細胞アッセイ 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.
動物実験 動物モデル Murine colon carcinoma xenografts MC26
投薬量 8 mg/kg
投与方法 Coadministration of Tariquidar (p.o.) with doxorubicin (5 mg/kg, i.v.)

カスタマーフィードバック

, , Vet Parasitol, 2015, 211(1-2):80-8.

Data from [Data independently produced by , , Biochem Pharmacol, 2016, 101:40-53.]

Data from [Data independently produced by , , Oncotarget, 2017, 8(5):7678-7690]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance [ Drug Resist Updat, 2024, 73:101066] PubMed: 38387283
Zosuquidar: An Effective Molecule for Intracellular Ca2+ Measurement in P-gp Positive Cells [ Int J Mol Sci, 2024, 25(6)3107] PubMed: 38542082
The net electrostatic potential and hydration of ABCG2 affect substrate transport [ Nat Commun, 2023, 14(1):5035] PubMed: 37596258
The net electrostatic potential and hydration of ABCG2 affect substrate transport [ Nat Commun, 2023, 14(1):5035] PubMed: 37596258
MDR1 Inhibition Reverses Doxorubicin-Resistance in Six Doxorubicin-Resistant Canine Prostate and Bladder Cancer Cell Lines [ Int J Mol Sci, 2023, 24(9)8136] PubMed: 37175843
MDR1 Inhibition Reverses Doxorubicin-Resistance in Six Doxorubicin-Resistant Canine Prostate and Bladder Cancer Cell Lines [ Int J Mol Sci, 2023, 24(9)8136] PubMed: 37175843
Establishment and Characterization of Multi-Drug Resistant p53-Negative Osteosarcoma SaOS-2 Subline [ Diagnostics -Basel), 2023, 13(16)2646] PubMed: 37627905
Establishment and Characterization of Multi-Drug Resistant p53-Negative Osteosarcoma SaOS-2 Subline [ Diagnostics (Basel), 2023, 13(16)2646] PubMed: 37627905
Panax notoginseng saponins reverse steroid resistance in lupus nephritis: Involvement of the suppression of exosomal P-gp levels from lymphocytes to glomerular endothelial cells [ Biochem Biophys Rep, 2023, 36:101568] PubMed: 38024866
Functional Blood-Brain Barrier Model with Tight Connected Minitissue by Liquid Substrates Culture [ Adv Healthc Mater, 2022, e2201984] PubMed: 36394091

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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