Tariquidar

Catalog No.S8028 Batch:S802802

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Technical Data

Formula

C38H38N4O6
Molecular Weight 646.73 CAS No. 206873-63-4
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 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]

Protocol (from reference)

Kinase Assay:

[1]
  • 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.
Cell Assay:

[3]
  • 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.
Animal Study:

[3]
  • Animal Models

    Murine colon carcinoma xenografts MC26

  • Dosages

    8 mg/kg

  • Administration

    Coadministration of Tariquidar (p.o.) with doxorubicin (5 mg/kg, i.v.)

Customer Product Validation

, , 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]

Data from [Data independently produced by , , Mol Med Rep, 2015, 12(6):8093-100.]

Selleck's Tariquidar has been cited by 50 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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