Tariquidar methanesulfonate hydrate

SKU: orb2655659

Description

A potent, specific P-gp inhibitor with Kd of 5.1 nM; potentiates the cytotoxicity of several drugs including doxorubicin, paclitaxel, etoposide, and vincristine in a panel of human MDR cell lines at 25-80 nM; exhibits potent i.v. and p.o. activity without apparently enhancing the plasma pharmacokinetics of paclitaxel or the toxicity of coadministered drugs.Breast Cancer Phase 2 Discontinued.

Key Properties

• CAS Number: 625375-83-9
• MW: 892.9887
• Purity: >98% (HPLC)
• Formula: C₄₀H₅₂N₄O₁₅S₂
• 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.CS(=O)(=O)O.CS(=O)(=O)O.O.O.O
• Target: P-glycoprotein
• Solubility: DMSO: ≥ 296 mg/mL; H2O: < 8.9 mg/mL

Bioactivity

• In Vivo:
  In mice bearing the intrinsically resistant MC26 colon tumors, coadministration of Tariquidar methanesulfonate, hydrate (XR9576 methanesulfonate, hydrate) potentiates the antitumor activity of Doxorubicin without a significant increase in toxicity; maximum potentiation is observed at 2.5-4.0 mg/kg dosed either i. v. or p.o. In addition, coadministration of Tariquidar (6-12 mg/kg p.o.) fully restores the antitumor activity of Paclitaxel, Etoposide, and Vincristine against two highly resistant MDR human tumor xenografts (2780AD, H69/LX4) in nude mice. Tariquidar is found to also significantly potentiate the antitumor activity of doxorubicin against s. c. MC26 tumors In vivo.
• In Vitro:
  Tariquidar methanesulfonate, hydrate (XR9576 methanesulfonate, hydrate) is a potent modulator of P-gp mediated [3H]-Vinblastine and [3H]-Paclitaxel transport as it increases the steady-state accumulation of these cytotoxics in CHrB30 cells to levels observed in non-P-gp-expressing AuxB1 cells (EC50 = 487±50 nM). [3H]-Tariquidar binds to CHrB30 membranes with the highest affinity (Kd=5.1±0.9 nM, n=7) and a binding capacity (Bmax) of 275±15 pmol/mg membrane protein. In contrast to the parental cell line, the accumulation of [3H]-Vinblastine is increased in a dose-dependent fashion by the modulators XR9576 (EC50 = 487±50 nM). The MDR modulator Tariquidar is able to inhibit 60-70% of the vanadate-sensitive ATPase activity, with potent IC50 value of 43±9 nM. Tariquidar (XR9576) potentiates the cytotoxicity of several drugs including Doxorubicin, Paclitaxel, Etoposide, and Vincristine; complete reversal of resistance is achieved in the presence of 25-80 nM Tariquidar. Tariquidar is a potent inhibitor of photoaffinity labeling of P-gp by [3H]Azidopine implying a direct interaction with the protein.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

XR 9576 | XR-9576 | XR9576

Quick Database Links

Gene Symbol

P-glycoprotein