What is the P-glycoprotein role in multi drug resistant cancers?
What is the P-glycoprotein role in multi drug resistant cancers?
P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs.
What does a glycoprotein inhibitor do?
Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors are a class of drugs that work by preventing the formation of blood clots by inhibiting the action of platelets.
How does verapamil inhibit P-gp?
The calcium-channel blocker verapamil is a known inhibitor of P-glycoprotein and may function to block P-glycoprotein-modulated efflux of antiepileptic drugs in the brain, thereby raising the intracellular concentration of antiepileptic drugs and ultimately decreasing seizure burden in patients with refractory epilepsy …
How do you think this overexpression of P-glycoprotein may have happened?
However, overexpression of P-gp may be induced by selection and/or adaptation of cells during exposure to anticancer drugs; this particular example is known as acquired P-gp-mediated MDR. Drugs that are potential inducers of P-gp are often substrates of this transporter.
Is digoxin a Pgp inhibitor?
Conclusions—Quinidine and digoxin are both substrates for P-glycoprotein, and quinidine is a potent inhibitor of digoxin transport in vitro.
What drugs should not be taken with colchicine?
The risk may be increased if other drugs that may also cause rhabdomyolysis are taken along with colchicine. Some affected drugs include: digoxin, gemfibrozil, pravastatin, simvastatin, among others. This medication may interfere with certain laboratory tests, possibly causing false test results.
What is the clinical relevance of P-glycoprotein P-gp?
The drug efflux transporter P-glycoprotein (P-gp) is known to confer multidrug resistance in cancer chemotherapy. Because of its expression and localization, it has been suggested that P-gp plays an important role in cancer chemotherapy, intestinal absorption, and brain uptake.
What is the impact of P-glycoprotein P-gp at the blood brain barrier?
Purpose: P-glycoprotein (Pgp) is an efflux transporter involved in transport of several compounds across the blood-brain barrier (BBB). Loss of Pgp function with increasing age may be involved in the development of age-related disorders, but this may differ between males and females.
What are CYP3A inhibitors?
CYP3A inducers include the glucocorticoids, rifampin, carbamazepine, phenobarbital, and phenytoin. Among the many significant CYP3A inhibitors are grapefruit juice, erythromycin, ketoconazole, clarithromycin, and verapamil.
Is it possible to reverse MDR by inhibiting P-glycoprotein?
There are currently no approved drugs available for clinical use in cancer chemotherapies to reverse MDR by inhibiting P-glycoprotein. Using computational studies, we previously identified several compounds that inhibit P-gp by targeting its nucleotide binding domain and avoiding its drug binding domains.
What is the pathophysiology of multidrug resistance (MDR)?
Despite advances in chemotherapies against cancer, multidrug resistance (MDR) remains a major obstacle to positive therapeutic outcomes in adult 1, 2, 3 as well as pediatric cancers 4. The most common mechanism of MDR is overexpression of drug efflux transporters of the ATP binding cassette (ABC) family.
Can P-gp inhibitors be used to re-sensitize MDR cancer cells?
Protein expression analyses showed that the compounds did not downregulate P-gp expression under the conditions used for re-sensitizing the MDR cancer cells. These properties of the P-gp inhibitors studied here make them attractive leads for further development.
Are there any compounds that inhibit P-gp?
Using computational studies, we previously identified several compounds that inhibit P-gp by targeting its nucleotide binding domain and avoiding its drug binding domains. Several of these compounds showed successful MDR reversal when tested on a drug resistant prostate cancer cell line.
