PgpRules: a decision tree based prediction server for P-glycoprotein substrates and inhibitors

2019 ◽  
Vol 35 (20) ◽  
pp. 4193-4195 ◽  
Author(s):  
Pei-Hua Wang ◽  
Yi-Shu Tu ◽  
Yufeng J Tseng
Keyword(s):  
Regression Tree ◽  
Structural Features ◽  
Classification And Regression Tree ◽  
Supplementary Information ◽  
Glycoprotein P ◽  
Toxic Compounds ◽  
P Glycoprotein ◽  
Transporter Family ◽  
Prediction Server ◽  
Pumping Activity

Abstract Summary P-glycoprotein (P-gp) is a member of ABC transporter family that actively pumps xenobiotics out of cells to protect organisms from toxic compounds. P-gp substrates can be easily pumped out of the cells to reduce their absorption; conversely P-gp inhibitors can reduce such pumping activity. Hence, it is crucial to know if a drug is a P-gp substrate or inhibitor in view of pharmacokinetics. Here we present PgpRules, an online P-gp substrate and P-gp inhibitor prediction server with ruled-sets. The two models were built using classification and regression tree algorithm. For each compound uploaded, PgpRules not only predicts whether the compound is a P-gp substrate or a P-gp inhibitor, but also provides the rules containing chemical structural features for further structural optimization. Availability and implementation PgpRules is freely accessible at https://pgprules.cmdm.tw/. Supplementary information Supplementary data are available at Bioinformatics online.

Significance and Mechanisms of P-glycoprotein in Central Nervous System Diseases

2019 ◽  
Vol 20 (11) ◽  
pp. 1141-1155 ◽  
Author(s):  
Liangliang Huang ◽  
Binbin Li ◽  
Xiang Li ◽  
Ge Liu ◽  
Rui Liu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Migration ◽  
Immune Cell ◽  
Microglia Activation ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Transporter Family ◽  
The Central Nervous System ◽  
Immune Cell Migration

P-glycoprotein (P-gp) is a member of ATP-Binding Cassette (ABC) transporter family. Because of its characteristic luminal surface location, high transport potency and structural specificity, Pgp is regarded as a selective gatekeeper of the Blood Brain Barrier (BBB) to prevent the entry of toxins or unwanted substances into the brain. In recent years, increasing evidence has shown that P-gp is involved in the immune inflammatory response in the Central Nervous System (CNS) disorders by regulating microglia activation, and mediating immune cell migration. Furthermore, Glucocorticoid Receptor (GR) may play a crucial role in P-gp-mediated microglia activation and immune cell migration via GR-mediated mRNA decay. In this article, we will review P-gp structure, distribution, function, regulatory mechanisms, inhibitors and effects of P-gp in the pathogenesis of several CNS diseases and will discuss the role of P-gp in microglia activation, immune cell migration and the relationship with cytokine secretion.

P-glycoprotein interfering agents potentiate ivermectin susceptibility in ivermectin sensitive and resistant isolates ofTeladorsagia circumcinctaandHaemonchus contortus

Parasitology ◽  
2009 ◽  
Vol 136 (9) ◽  
pp. 1081-1088 ◽  
Author(s):  
D. J. BARTLEY ◽  
H. McALLISTER ◽  
Y. BARTLEY ◽  
J. DUPUY ◽  
C. MÉNEZ ◽  
...  
Keyword(s):  
Epithelial Cell Line ◽  
Transport Activity ◽  
Free Living ◽  
Glycoprotein P ◽  
Intestinal Nematode ◽  
Nematode Parasites ◽  
Teladorsagia Circumcincta ◽  
P Glycoprotein ◽  
Transporter Family

SUMMARYP-glycoprotein (P-gp) homologues, belonging to the ATP Binding Cassette (ABC) transporter family, are thought to play an important role in the resistance of gastro-intestinal nematode parasites against macrocyclic lactones. The aim of this study was to investigate the influence of various P-gp interfering compounds on the efficacy of ivermectin (IVM) in sensitive and resistant nematode isolates. The feeding of IVM resistant and sensitiveTeladorsagia circumcinctaandHaemonchus contortusfirst-stage larvae (L1) was assessed using a range of IVM concentrations (0·08–40 nm) with or without P-gp inhibitors: valspodar, verapamil, quercetin, ketoconazole and pluronic P85. The P-gp inhibitors were selected on the basis of their ability to interfere with P-gp transport activity in an epithelial cell line over-expressing murine P-gp. In the presence of P-gp interfering agents, thein vitrosusceptibility to IVM of both sensitive and resistant isolates ofT. circumcinctaandH. contortuswas increased. These results show that compounds interfering with P-gp transport activity could enhance IVM efficacy in sensitive isolates, and also restore IVM sensitivity in resistant nematodes. These results support the view that ABC transporters can play an important role in resistance to IVM, at least in the free-living stages of these economically important gastro-intestinal nematodes.

Correlation between P-glycoprotein (P-gp) expression in parathyroid and Tc-99m MIBI parathyroid image findings

2001 ◽  
Vol 28 (8) ◽  
pp. 929-933 ◽  
Author(s):  
Shung-Shung Sun ◽  
Yu-Chien Shiau ◽  
Cheng-Chieh Lin ◽  
Albert Kao ◽  
Cheng-Chun Lee
Keyword(s):  
Glycoprotein P ◽  
P Glycoprotein

GCS-Pupil Score Has a Stronger Association with Mortality and Poor Functional Outcome than GCS Alone in Pediatric Severe Traumatic Brain Injury

2021 ◽  
pp. 1-8
Author(s):  
Binod Balakrishnan ◽  
Heather VanDongen-Trimmer ◽  
Irene Kim ◽  
Sheila J. Hanson ◽  
Liyun Zhang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcome ◽  
Cerebral Performance Category ◽  
Regression Tree ◽  
Classification And Regression Tree ◽  
Continuous Variables ◽  
Poor Functional Outcome ◽  
Severity Scores ◽  
Pupil Reactivity

<b><i>Background:</i></b> The Glasgow Coma Scale (GCS), used to classify the severity of traumatic brain injury (TBI), is associated with mortality and functional outcomes. However, GCS can be affected by sedation and neuromuscular blockade. GCS-Pupil (GCS-P) score, calculated as GCS minus Pupil Reactivity Score (PRS), was shown to better predict outcomes in a retrospective cohort of adult TBI patients. We evaluated the applicability of GCS-P to a large retrospective pediatric severe TBI (sTBI) cohort. <b><i>Methods:</i></b> Admissions to pediatric intensive care units in the Virtual Pediatric Systems (VPS, LLC) database from 2010 to 2015 with sTBI were included. We collected GCS, PRS (number of nonreactive pupils), cardiac arrest, abusive head trauma status, illness severity scores, pediatric cerebral performance category (PCPC) score, and mortality. GCS-P was calculated as GCS minus PRS. χ<sup>2</sup> or Fisher’s exact test and Mann-Whitney U test compared categorical and continuous variables, respectively. Classification and regression tree analysis identified thresholds of GCS-P and GCS along with other independent factors which were further examined using multivariable regression analysis to identify factors independently associated with mortality and unfavorable PCPC at PICU discharge. <b><i>Results:</i></b> Among the 2,682 patients included in the study, mortality was 23%, increasing from 4.7% for PRS = 0 to 80% for PRS = 2. GCS-P identified more severely injured patients with GCS-P scores 1 and 2 who had worse outcomes. GCS-P ≤ 2 had higher odds for mortality, OR = 68.4 (95% CI = 50.6–92.4) and unfavorable PCPC, OR = 17.3 (8.1, 37.0) compared to GCS ≤ 5. GCS-P ≤ 2 also had higher specificity and positive predictive value for both mortality and unfavorable PCPC compared to GCS ≤ 5. <b><i>Conclusions:</i></b> GCS-P, by incorporating pupil reactivity to GCS scoring, is more strongly associated with mortality and poor functional outcome at PICU discharge in children with sTBI.

Molecular docking studies of tea (Thea sinensis Linn.) polyphenols inhibition pattern with Rat P-glycoprotein

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Babar Ali ◽  
Qazi Mohammad Sajid Jamal ◽  
Showkat R. Mir ◽  
Saiba Shams ◽  
Mohammad Amjad Kamal
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Oral Administration ◽  
Docking Studies ◽  
Vital Role ◽  
Glycoprotein P ◽  
High Affinity ◽  
P Glycoprotein ◽  
Inhibition Pattern

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

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