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P-glycoproteins

To account for the observed broad substrate specificities for both CYP3A4 and P-gp, the presence of multiple drug binding sites has been proposed. The first experimentally determined signs of complex kinetic [Pg.356]

The ascorbate transporter SVCTl has been shown to be inhibited by some flavonols such as quercetin but less so by the related catechins. The absence of the ketone at the 4-position of the C ring has a dramatic negative effect on the potency of inhibition, suggesting that a key hydrogen-bonding [Pg.361]

Juranka, P. F., Za.stawny, R. L., and Ling, V., 1989. P-Glycoprotein Multidrug-resistance and a superfamily of membrane-a.s.sociated tran.sport protein.s. The FASEByowrna/3 2583-2592. [Pg.325]

Inhibition of human multidrug resistance P-glycoprotein 1 was investigated by analogs of a potent. 5-opioid antagonist, including (35, 1 lu5)-3-[(4-hydroxy-2,6-dimethylphenyl)methyl]-11,11 u-dihydro-2//-pyrazino[l, 1-b] isoquinoline-l,4(3//,6//)-dione (OIMIIO). Opioid antagonist activity of... [Pg.324]

Gottesman MM, Ling V (2006) The Molecular basis of multidrug resistance in cancer tlie early years of P-glycoprotein research. FEBS Lett 580 998-1009... [Pg.8]

P-glycoprotein (P-gp) works as a transporter at the intestinal mucosa pumping drugs out into the lumen. Absorption of P-gp substrates, such as digoxin, cyclosporine, etc., can be increased by inhibitors of P-gp and reduced by inducers. [Pg.448]

Storch CH, Theile D, Lindenmaier H, Haefeh WE, Weiss J (2007) Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein, Biochem Pharmacol 73 1573-1581... [Pg.50]

An example of a valid, easily interpretable QSAR is that relating to P-glycoprotein-regulated multidrug resistance reversal (MDRR) by phenothi-azines [43] ... [Pg.477]

A key requirement of QSAR is that the compounds used in the modeling and prediction processes should have the same mechanism of action, and for this reason most QSAR studies are made with congeneric series of compounds. However, if a diverse set of compounds can reasonably be assumed to have the same mechanism of action, QSAR modeling can justihably be carried out. For example, Dearden et al. [43] developed a QSAR for the ratio of brain levels of 22 very diverse drugs in the wild-type mouse and the P-glycoprotein knockout mouse (R+/ ) ... [Pg.479]

Dearden JC, AI-Noobi A, Scott AC, Thomson SA. QSAR studies on P-glycoprotein-regulated multidrug resistance and on its reversal by phenothia-zines. SAR QSAR Environ Res 2003 14 447-54. [Pg.490]

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. [Pg.500]

Lin JH and Yamazaki M. Role of P-glycoprotein in pharmacokinetics clinical implications. Clin Pharmacokinet 2005 A2 59-98. [Pg.510]

Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci USA 1997 94 2031-5. [Pg.510]

Polli JW, Jarrett JL, Studenberg SD, Humphreys JE, Dennis SW, Brouwer KR, et al. Role of P-glycoprotein on the CNS disposition of amprenavir (141W94), an HIV protease inhibitor. Pharm Res 1999 16 1206-12. [Pg.510]

Ekins S, Kim RB, Leake BE, Dantzig AH, Schuetz E, Lan LB, et al. Application of three dimensional quantitative structure-activity relationships of P-glycoprotein inhibitors and substrates. Mol Pharmacol 2002 61 974-981. [Pg.510]

Pajeva IK and Wiese M. Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance explanation of structural variety (hypothesis). J Med Chem 2002 45 5671-5686. [Pg.511]

Yates CR, Chang C, Kearbey JD, Yasuda K, Schuetz EG, Miller DD, et al. Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res 2003 20 1794-803. [Pg.511]

The GIT supplements the kidney in the elimination of wastes and toxins. The P-glycoprotein of enterocytes, which is implicated in multi-drug resistance, plays a critical role. This export carrier exhibits varying responses to the different polyphenols present in green tea (Wang et al, 2002), and is inhibited by one or more components of grapefruit juice (Wagner et al, 2001). It is... [Pg.168]

EDWARDS D J, FITZSIMMONS M E, SCHUETZ E G, YASUDA K, DUCHARME M P, WARBASSE L H, WOSTER p M, SCHUETZ J D, WATKINS p (1999) 6, 7 -Dihydroxybergamottm in grapefruit juice and Seville orange juice effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther. 65 237-44. [Pg.177]

WANG E, BARECKi-ROACH M, JOHNSON w (2002) Elevation of P-glycoprotein function by a catechin in green tea. Biochem Biophys Res Commun. 297 412. [Pg.186]

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ADMET properties efflux by P-glycoprotein

Aspects of P-Glycoprotein Regulation

Biliary Excretion Mediated by P-Glycoprotein

Efflux by P-glycoprotein

Efflux transporter P-glycoprotein

Function of P-Glycoprotein

Intestinal P-glycoprotein

MDR1 P-glycoprotein

MDRl/P-glycoprotein

Membrane P-glycoprotein

P glycoprotein efflux

P-glycoprotein drug efflux pump

P-glycoprotein efflux pump

P-glycoprotein expression

P-glycoprotein family

P-glycoprotein gene

P-glycoprotein in tumor

P-glycoprotein inducers

P-glycoprotein inhibition

P-glycoprotein inhibitors

P-glycoprotein interactions

P-glycoprotein multidrug

P-glycoprotein overexpression

P-glycoprotein pump

P-glycoprotein substrates

P-glycoprotein transport

P-glycoprotein transporter

P-glycoprotein, multidrug transporter

P-glycoproteine efflux pump

P-selectin glycoprotein ligand

Predicting Substrate Properties for P-Glycoprotein

Sister of P-glycoprotein

Structure, of P-glycoprotein

What Properties Are Shared by Drugs that Interact with P-Glycoprotein

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