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Synonyms | XR9576 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C38H38N4O6 |
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分子量 | 646.73 | CAS No. | 206873-63-4 | |
Solubility (25°C)* | 体外 | DMSO | 8 mg/mL (12.36 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <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. |
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. |
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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] |
キナーゼアッセイ | Steady-state drug accumulation assay | |
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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. |
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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.) |
, , 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]
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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