Tariquidar

SKU: orb1300901

Description

Tariquidar (XR9576) is a potent, non-competitive P-glycoprotein inhibitor with a Kd of 5.1 nM. It is widely used in vitro to reverse multidrug resistance in cancer cell lines and has been applied in vivo to investigate pharmacokinetic enhancement of chemotherapeutic agents.

Research Area

Neuroscience, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 206873-63-4
• MW: 646.73
• Purity: >99.99% (May vary between batches)
• Formula: C₃₈H₃₈N₄O₆
• SMILES: COc1cc2CCN(CCc3ccc(NC(=O)c4cc(OC)c(OC)cc4NC(=O)c4cnc5ccccc5c4)cc3)Cc2cc1OC
• Target: P-gp
• Solubility: DMSO:49.5 mg/mL (76.54 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (1.55 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  P-gp:5.1 nM(Kd)
• 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.
• 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 CHr<>/supB30 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. Tariquidar may inhibit other resistance mechanisms at higher concentrations. 1 μM Tariquidar abrogates ABCG2 (BCRP)-mediated resistance to camptothecins in vitro. 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. 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.
• Cell Research:
  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.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Tariquidar, Pgp, P-gp, P-gp (P-glycoprotein), P-glycoprotein, XR9576, XR-9576, XR 9576, Cluster of differentiation 243, CD243, ABCB1, Multidrug resistance protein 1, inhibit, Inhibitor, MDR1

Compound Identifiers

PubChem CID

148201