Tariquidar methanesulfonate hydrate

SKU: orb1708409

Description

Tariquidar methanesulfonate hydrate (XR9576) is a potent and selective inhibitor of the P-glycoprotein (P-gp) efflux pump. It is used in research to investigate P-gp function, particularly in overcoming multidrug resistance in cancer and modulating blood-brain barrier permeability in preclinical models.

Research Area

Neuroscience, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 625375-83-9
• MW: 947.04
• Purity: 98.13%
• Formula: C₄₀H₅₈N₄O₁₈S₂
• SMILES: O=C(C1=CN=C2C=CC=CC2=C1)NC3=CC(OC)=C(C=C3C(NC4=CC=C(CCN5CC6=CC(OC)=C(C=C6CC5)OC)C=C4)=O)OC.O=S(O)(C)=O.O=S(O)(C)=O.O.O.O.O.O.O
• Target: P-gp
• Solubility: H2O:4 mg/mL (4.22 mM);DMSO:200 mg/mL (211.18 mM)

Bioactivity

• Target IC50:
  P-gp:487 nM (EC50)|CHrB30 membranes:5.1 nM (Kd)|CHrB30 membranes:275 pmol/mg (Bmax)|ATPase (vanadate-sensitive):43 nM
• In Vivo:
  In a mouse model harboring MC26 colon tumors (with intrinsic resistance), combination with Tariquidar methanesulfonate hydrate potentiated the antitumor effects of doxorubicin without a significant increase in toxicity; potentiation was maximal at doses of 2.5-4.0 mg/kg (which can be administered intravenously or orally). The synergistic effect was maximized at a dose of 2.5-4.0 mg/kg (which can be administered intravenously or orally). In addition, oral administration of Tariquidar methanesulfonate hydrate at 6-12 mg/kg completely restored the antitumor activity of paclitaxel, etoposide, and vincristine against two highly resistant MDR human tumor xenograft tumors (2780AD and H69/LX4) in nude mice. It was also shown that in vivo Tariquidar methanesulfonate hydrate significantly potentiated the anticancer effect of doxorubicin against subcutaneous MC26 tumors.
• In Vitro:
  Tariquidar methanesulfonate hydrate is a potent P-gp-mediated inhibitor of [³H]-vincristine and [³H]-paclitaxel transport that elevates the accumulation of these drugs in CHrB30 cells to a level similar to that of AuxB1 cells that do not express P-gp (EC50 of 487 nM) . [³H]-Tariquidar methanesulfonate hydrate showed high binding affinity (Kd of 5.1 nM) on CHrB30 membranes and had a maximum binding capacity (Bmax) of 275 pmol/mg membrane protein. Tariquidar methanesulfonate hydrate significantly increased the intracellular accumulation of [³H]-vincristine (EC50 of 487 nM) through a dose-dependent effect compared to its parental cells. In addition, the multidrug resistance modifier Tariquidar methanesulfonate hydrate inhibited 60-70% of vanadate-sensitive ATPase activity with an IC50 of 43 nM.

Storage & Handling

• Storage: keep away from moisture | 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

Pgp, P-gp, XR9576 methanesulfonate hydrate, XR 9576 methanesulfonate hydrate

Compound Identifiers

PubChem CID

9897794