Tariquidar

• CAS: 206873-63-4
• Catalog Number: ACM206873634
• Category: Main Products
• Molecular Weight: 646.73
• Molecular Formula: C38H38N4O6

Case Study

Tariquidar-Loaded Hydroxyapatite for Enhanced Glioblastoma Therapy

Yu C-P, et al. European Journal of Pharmaceutics and Biopharmaceutics, 2024, 197, 114231.

Tariquidar (TQD), a potent P-glycoprotein (P-gp) inhibitor, has gained attention for its role in overcoming multidrug resistance (MDR) in glioblastoma (GBM) therapy. This study explored the use of stearic acid-modified hydroxyapatite (SA-HAP) as an advanced delivery platform for TQD in combination with temozolomide (TMZ). By leveraging the hydrophobic interaction between TQD and the SA-HAP carrier, an innovative formulation (SA-HAP-TQD) was developed to optimize drug delivery and therapeutic efficacy.
The SA-HAP carrier was synthesized via a co-precipitation method, using phosphoric acid, calcium hydroxide, and stearic acid under controlled pH and stirring conditions to achieve a Ca/P ratio of 1.67. The resultant SA-HAP particles were homogenized, suspended in Tween 80/PBS, and loaded with TQD via overnight stirring, producing a stable SA-HAP-TQD formulation.

Tariquidar-Loaded Nanostructured Lipid Carriers for Multidrug Resistance Reversal in Tumor Therapy

Kim CH, et al. Journal of Drug Delivery Science and Technology, 2022, 71, 103323.

This study investigated the co-delivery of Tariquidar (TRQ)and docetaxel (DTX) using nanostructured lipid carriers (NLCs) functionalized with polyethylene glycol (PEG) and RIPL peptide (P/R). The engineered formulation, TRQ-loaded P/R-functionalized NLCs (TRQ-P/R-N), demonstrated robust physicochemical stability, efficient drug encapsulation (>95%), and nano-sized dispersion (<210 nm).
The NLCs were synthesized via solvent emulsification evaporation, utilizing a blend of solid (Precirol ATO 5) and liquid (Labrafil M 1944 CS) lipids. Surface functionalization with DSPE-PEG3000 and DSPE-PEG2000-RIPL enhanced the biocompatibility and targeting capabilities of the carrier. The TRQ-P/R-N formulation exhibited a diffusion-controlled drug release profile and was stable under refrigeration for up to 4 weeks. Co-treatment with TRQ-P/R-N and DTX-P/R-N at a 1:1 w/w ratio achieved the highest synergy (combination index 0.285), significantly reversing P-gp-mediated MDR in MCF7/ADR cells.
TRQ-P/R-N enhanced intracellular accumulation of Rhodamine 123 and induced potent, dose-dependent cytotoxicity, increasing apoptosis and promoting G2/M cell cycle arrest. These results underscore the therapeutic potential of TRQ-loaded NLCs as a targeted strategy to overcome MDR in cancer therapy, specifically by inhibiting P-gp activity and enhancing chemotherapeutic efficacy.

Tariquidar for Overcoming Drug Resistance in Epilepsy through P-glycoprotein Inhibition

Ilyas-Feldmann M, et al. Seizure: European Journal of Epilepsy, 2024, 119, 44-51.

Tariquidar (TQD), a selective P-glycoprotein (P-gp) inhibitor, shows significant potential in addressing drug resistance in epilepsy by enhancing brain entry of antiseizure medications (ASMs). P-gp, a key efflux transporter at the blood-brain barrier, reduces ASM efficacy by actively extruding these drugs from the brain. Co-administration of TQD with ASMs represents a promising strategy to counteract resistance.
A multi-center cohort study assessed the tolerability of single-dose intravenous TQD in drug-resistant epilepsy patients and healthy controls at doses ranging from 2 to 8 mg/kg. At 2-3 mg/kg, TQD was well-tolerated, with mild adverse events reported in only a minority of participants (approximately 4% in epilepsy patients and 33% in controls). Higher doses administered to controls showed similar tolerability profiles. Increased ASM levels in the brain after TQD administration were associated with improved ASM efficacy, suggesting effective P-gp inhibition at the blood-brain barrier.

Tariquidar Enhances the Efficacy of Antidotes in Organophosphate-Induced Seizures

Meerhoff GF, et al. NeuroToxicology, 2018, 68, 167-176.

Tariquidar (TQD), a potent P-glycoprotein (P-gp) inhibitor, demonstrates significant promise in optimizing treatments for organophosphate (OP)-induced seizures. In a rat model exposed to the nerve agent soman, the inclusion of TQD (7.5 mg/kg i.v.) alongside standard antidotes-HI-6 (125 mg/kg) and atropine sulfate (3 mg/kg)-resulted in rapid normalization of EEG activity and cessation of seizure-associated behaviors, particularly when TQD was administered 1 minute post-exposure. Co-administration of TQD with diazepam further amplified these effects, even when administered 40 minutes after seizure onset. The combined therapy reduced neuronal loss, microglial activation, and astrogliosis, particularly in the piriform cortex, amygdala, and entorhinal cortex.
These findings highlight TQD's synergistic interaction with atropine, a known P-gp substrate, in enhancing antidotal efficacy. This study underscores the potential of TQD to improve late-stage interventions for OP poisoning, providing a compelling case for its inclusion in combination therapies aimed at mitigating the severe neuropathology associated with nerve agent exposure.