tariquidar

Tariquidar, also known as XR9576, is a synthetic small molecule that acts as a selective inhibitor of the human P-glycoprotein (MDR1) drug efflux transporter. It was developed as a chemosensitizer intended to overcome multidrug resistance in cancer by increasing the intracellular concentrations of co-administered chemotherapeutic agents.

Mechanism of action remains the central feature: tariquidar binds to P-glycoprotein and inhibits its drug efflux activity, thereby reducing the expulsion of P-gp substrates from cancer cells. This can lead to higher intracellular exposure to chemotherapy drugs and, in theory, improved anticancer activity. It is designed for intravenous administration and has been studied in various dosing regimens in clinical trials.

Clinical development and status: Tariquidar reached phase I and II trials in several cancers, including ovarian cancer, non-small cell lung cancer, breast cancer, and leukemia, typically in combination with chemotherapeutic agents such as paclitaxel, docetaxel, vinorelbine, and doxorubicin. While pharmacokinetic studies often showed increased systemic exposure to co-administered drugs, clinical outcomes were not consistently superior, and safety concerns emerged (including hematologic toxicity and cardiovascular events). As a result, development did not advance to regulatory approval for cancer indications.

Current status: Tariquidar has not been approved by major regulatory authorities. Research has continued in the broader field of resistance reversal, with attention to optimizing safety, patient selection, and combination strategies, but tariquidar itself has not become an approved therapy.