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<p><b>New page</b></p><div>[[File:Atlas-legend.png|thumb|Atlas-legend.png]] '''P-glycoprotein''' ('''P-gp'''), also known as '''multidrug resistance protein 1''' ('''MDR1''') or '''ATP-binding cassette sub-family B member 1''' ('''ABCB1'''), is a well-characterized [[protein]] that functions as a [[transmembrane]] [[ATPase]] [[efflux pump]]. It plays a crucial role in the [[pharmacokinetics]] of many drugs by transporting a wide variety of substrates across [[cell membranes]].<br />
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==Structure==<br />
P-glycoprotein is a member of the [[ATP-binding cassette transporters|ATP-binding cassette (ABC) transporter]] family. It consists of two homologous halves, each containing six [[transmembrane domains]] and an [[ATP-binding domain]]. The transmembrane domains form a pathway through which substrates are transported, while the ATP-binding domains provide the energy required for the transport process through [[ATP hydrolysis]].<br />
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==Function==<br />
P-glycoprotein is primarily involved in the [[efflux]] of xenobiotics and endogenous compounds out of cells. It is expressed in various tissues, including the [[liver]], [[kidney]], [[intestine]], [[blood-brain barrier]], and [[placenta]]. By pumping out potentially harmful substances, P-glycoprotein protects tissues from toxic insults and plays a significant role in [[drug metabolism]] and [[drug resistance]].<br />
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==Clinical Significance==<br />
P-glycoprotein is a key player in the phenomenon of [[multidrug resistance]] (MDR) in [[cancer]] therapy. Overexpression of P-gp in [[tumor]] cells can lead to decreased intracellular concentrations of chemotherapeutic agents, rendering them less effective. Inhibitors of P-glycoprotein are being studied as potential adjuvants to improve the efficacy of anticancer drugs.<br />
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Additionally, P-glycoprotein affects the [[absorption]], [[distribution]], and [[excretion]] of many drugs, influencing their [[bioavailability]] and [[therapeutic index]]. It is also involved in the [[blood-brain barrier]], limiting the entry of drugs into the [[central nervous system]].<br />
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==Genetics==<br />
The gene encoding P-glycoprotein is known as [[ABCB1]]. Genetic polymorphisms in ABCB1 can affect the expression and function of P-glycoprotein, leading to interindividual variability in drug response and toxicity.<br />
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==Research and Development==<br />
Ongoing research aims to better understand the structure-function relationship of P-glycoprotein, its role in drug resistance, and the development of inhibitors to modulate its activity. Advances in [[cryo-electron microscopy]] and [[molecular dynamics simulations]] have provided insights into the conformational changes associated with substrate transport and ATP hydrolysis.<br />
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==See Also==<br />
* [[ATP-binding cassette transporters]]<br />
* [[Multidrug resistance]]<br />
* [[Blood-brain barrier]]<br />
* [[Pharmacokinetics]]<br />
* [[Drug metabolism]]<br />
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==References==<br />
{{Reflist}}<br />
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==External Links==<br />
{{Commons category|P-glycoprotein}}<br />
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[[Category:Proteins]]<br />
[[Category:Transmembrane transporters]]<br />
[[Category:ATP-binding cassette transporters]]<br />
[[Category:Pharmacokinetics]]<br />
[[Category:Drug resistance]]<br />
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