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Probenecid is an inhibitor of organic anion transport and MRP [1] [2]. Also, probenecid inhibited pannexin-1 channel with IC50 value of 150μM [3].

Multidrug resistance-associated proteins (MRPs) are ATP-binding cassette (ABC) transporters that transport various molecules across cellular membranes and are involved in multi-drug resistance.

Probenecid is an inhibitor of organic anion transport, MRP and pannexin-1 channel. In MRP-overexpressing HL60/AR and H69/AR tumor cell lines, probenecid reversed resistance to daunorubicin (DNR) and vincristine (VCR) in a concentration-dependent way [1]. In wild-type AML-2 cells, probenecid increased the MRP levels in a dose- and time-dependent way. In MRP-overexpressing AML cells, probenecid exhibited a significant chemosensitizing effect. These results suggested that probenecid functioned as an effective chemosensitizer of multidrug resistance (MDR) tumor cells but also an MRP activator [2].

In ischemia/reperfusion (I/R) injury rats, probenecid protected against CA1 neuronal death. Probenecid strengthened the upregulation of Hsp70 and inhibited the expression of calpain-1 and the released of cathepsin B. Also, probenecid inhibited the proliferation of astrocytes and microglia [4].

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