PGP Inhibitors
P-glycoprotein (PGP), also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1), is a critical efflux transporter that plays a significant role in the cellular export of various substrates across the cell membrane. This protein is extensively expressed in the tissues of the liver, pancreas, kidneys, intestines, and the blood-brain barrier, where it serves a pivotal function in the protection of cells by pumping out harmful compounds, including xenobiotics and endogenous metabolites. The activity of PGP is driven by ATP hydrolysis, which provides the energy required for the translocation of substrates from the intracellular to the extracellular space, thereby contributing to the regulation of absorption, distribution, metabolism, and excretion of these molecules. Through its action, PGP plays an essential role in influencing the bioavailability and disposition of many compounds within the body.
The inhibition of PGP can significantly alter the cellular concentration of its substrates, leading to an accumulation of compounds that are normally effluxed by this transporter. Inhibition occurs through various mechanisms, including direct binding to the transporter, which prevents substrate interaction, and modulation of the ATPase activity, which is necessary for the energy-dependent efflux function of PGP. Some inhibitors work by interfering with the transporter's ability to hydrolyze ATP, effectively halting the energy supply that drives the efflux activity. Others may induce conformational changes in the protein structure, hindering its capacity to bind or transport substrates. This inhibition can influence the pharmacokinetics of substrates by increasing their intracellular concentrations and affecting their overall distribution and elimination profiles. Given the broad substrate specificity of PGP, its inhibition can impact the cellular handling of a wide range of compounds, highlighting the importance of understanding these interactions to predict and manage the effects on substrate disposition effectively.
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Verapamil | 52-53-9 | sc-507373 | 1 g | $367.00 | ||
Verapamil functions as a P-glycoprotein (PGP) inhibitor by directly binding to the transporter, which leads to a reduction in PGP's efflux capacity. This inhibition mechanism allows Verapamil to prevent the efflux of substrates across cell membranes, thereby increasing their intracellular concentrations. | ||||||
Cyclosporin A | 59865-13-3 | sc-3503 sc-3503-CW sc-3503A sc-3503B sc-3503C sc-3503D | 100 mg 100 mg 500 mg 10 g 25 g 100 g | $62.00 $90.00 $299.00 $475.00 $1015.00 $2099.00 | 69 | |
Cyclosporine A exerts its inhibitory effect on PGP by binding with high affinity to the transporter, thereby interfering with its substrate binding sites. This action blocks the efflux activity of PGP, leading to an accumulation of PGP substrates within the cells, independent of its immunosuppressive functions.. | ||||||
Quinidine | 56-54-2 | sc-212614 | 10 g | $102.00 | 3 | |
Quinidine inhibits PGP by competitively interacting with the substrate binding domains of the transporter. This competitive inhibition reduces the efflux of PGP substrates, thereby increasing their availability inside the cell. | ||||||
Ketoconazole | 65277-42-1 | sc-200496 sc-200496A | 50 mg 500 mg | $62.00 $260.00 | 21 | |
Ketoconazole targets PGP through a mechanism that involves the inhibition of the transporter's ATPase activity. By reducing the energy available for substrate efflux, Ketoconazole effectively increases the intracellular concentration of PGP substrates. | ||||||
Elacridar | 143664-11-3 | sc-207613A sc-207613 sc-207613B sc-207613C sc-207613D | 5 mg 10 mg 50 mg 100 mg 1 g | $96.00 $111.00 $403.00 $515.00 $2555.00 | 19 | |
Elacridar specifically inhibits PGP by binding to the transporter and blocking its ability to efflux substrates. This direct inhibition leads to an enhanced retention of substrates within cells, demonstrating its potential to influence the pharmacokinetic profiles of various compounds. | ||||||