What is ABCG2 pump?
ATP-binding cassette (ABC), sub-family G, isoform 2 protein (ABCG2, also known as breast cancer resistance protein, BCRP) is a drug efflux pump and an important member of the ABC transporter superfamily. ABCG2 was identified independently by three separate groups in 1998 and 1999 [3–5].
What are ABCG2 pump inhibitors?
As an efflux pump exhibiting a broad substrate specificity localized on cellular plasma membrane, ABCG2 excretes a variety of endogenous and exogenous substrates including chemotherapeutic agents, such as mitoxantrone and several tyrosine kinase inhibitors.
What is antibiotic efflux?
Drug efflux is a key mechanism of resistance in Gram-negative bacteria. These systems pump solutes out of the cell. Efflux pumps allow the microorganisms to regulate their internal environment by removing toxic substances, including antimicrobial agents, metabolites and quorum sensing signal molecules.
What is PGP substrate?
Efflux transporters such as P-glycoprotein play an important role in drug transport in many organs. Important substrates of P-glycoprotein include calcium channel blockers, cyclosporin, dabigatran etexilate, digoxin, erythromycin, loperamide, protease inhibitors and tacrolimus.
What is efflux pump system?
Efflux pumps are transport proteins involved in the extrusion of toxic substrates (including virtually all classes of clinically relevant antibiotics) from within cells into the external environment. These proteins are found in both Gram-positive and -negative bacteria as well as in eukaryotic organisms.
What is tetracycline efflux pump?
Efflux is the most common mechanism of tetracycline resistance. Class A tetracycline efflux pumps, which often have high prevalence in Enterobacteriaceae, are encoded by tet(A) and tet(A)-1 genes. These genes have two potential start codons, GTG and ATG, located upstream of the genes.
What does P-glycoprotein do?
P-glycoprotein, the most extensively studied ATP-binding cassette (ABC) transporter, functions as a biological barrier by extruding toxins and xenobiotics out of cells. In vitro and in vivo studies have demonstrated that P-glycoprotein plays a significant role in drug absorption and disposition.
How do you remember CYP interactions?
Cytochrome P450 (CYP450) enzymes can be inhibited or induced by some drugs, resulting in significant drug interactions that can cause unanticipated adverse reactions or therapeutic failures. An easy way to remember the mnemonic is; CRAP GPs spend all day on SICKFACES.com.
Is pantoprazole a BCRP inhibitor?
In Sf9-BCRP vesicles, pantoprazole and omeprazole inhibited MTX transport (IC50 13 microm and 36 microm, respectively).
Where are efflux pumps found?
Efflux pumps are proteinaceous transporters localized in the cytoplasmic membrane of all kinds of cells. They are active transporters, meaning that they require a source of chemical energy to perform their function.
Which is an exogenous substrate of ABCG2 efflux pump?
As an efflux pump exhibiting a broad substrate specificity localized on cellular plasma membrane, ABCG2 excretes a variety of endogenous and exogenous substrates including chemotherapeutic agents, such as mitoxantrone and several tyrosine kinase inhibitors.
How is ABCG2 related to breast cancer resistance?
The ATP-binding cassette transporter G2 (ABCG2; also known as breast cancer resistance protein, BCRP) has been suggested to be involved in clinical multidrug resistance (MDR) in cancer like other ABC transporters such as ABCB1 (P-glycoprotein).
What kind of ultracentrifugation is used for ABCG2?
For ABCG2, sucrose density gradient ultracentrifugation for the isolation of plasma membrane fraction is generally employed to prepare plasma membrane vesicles from ABCG2-expressing cells (related notes are inscribed in the legend of Figure 1 ).
Which is the first inhibitor of ABCG2 in humans?
The first ABCG2 inhibitor reported was FTC, a mycotoxin produced by Aspergillus fumigatus (Rabindran et al., 1998, 2000). The in vivo use of FTC was unfortunately precluded due to its neurotoxicity.
