scholarly journals Data-Driven Ensemble Docking to Map Molecular Interactions of Steroid Analogs with Hepatic Organic Anion Transporting Polypeptides

2021 ◽  
Author(s):  
Alzbeta Tuerkova ◽  
Orsolya Ungvári ◽  
Réka Laczkó-Rigó ◽  
Erzsébet Mernyák ◽  
Gergely Szakács ◽  
...  
Keyword(s):  
Molecular Interactions ◽  
Organic Anion ◽  
Data Driven ◽  
Organic Anion Transporting Polypeptides ◽  
Ensemble Docking

Hepatic organic anion transporting polypeptides mediate disposition of milk thistle flavonolignans and pharmacokinetic silymarin‐drug interactions

2021 ◽  
Author(s):  
Katherine D. Lynch ◽  
Michelle L. Montonye ◽  
Dan‐Dan Tian ◽  
Tarana Arman ◽  
Victoria O. Oyanna ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Milk Thistle ◽  
Organic Anion Transporting Polypeptides

scholarly journals Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 834
Author(s):  
Anima M. Schäfer ◽  
Henriette E. Meyer zu Schwabedissen ◽  
Markus Grube
Keyword(s):  
Organic Anion ◽  
Physiological Role ◽  
Point Of View ◽  
Efflux Transporters ◽  
Organic Anion Transporting Polypeptides ◽  
Current State ◽  
P Glycoprotein ◽  
The Central Nervous System ◽  
And Function ◽  
Uptake Transporters

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.

scholarly journals A generalizable data-driven multicellular model of pancreatic ductal adenocarcinoma

GigaScience ◽  
2020 ◽  
Vol 9 (7) ◽  
Author(s):  
Boris Aguilar ◽  
David L Gibbs ◽  
David J Reiss ◽  
Mark McConnell ◽  
Samuel A Danziger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Interactions ◽  
Positive Impact ◽  
Stellate Cells ◽  
The Cancer Genome Atlas ◽  
Data Driven ◽  
Ductal Adenocarcinoma ◽  
Modeling Framework ◽  
Pertinent Data

Abstract Background Mechanistic models, when combined with pertinent data, can improve our knowledge regarding important molecular and cellular mechanisms found in cancer. These models make the prediction of tissue-level response to drug treatment possible, which can lead to new therapies and improved patient outcomes. Here we present a data-driven multiscale modeling framework to study molecular interactions between cancer, stromal, and immune cells found in the tumor microenvironment. We also develop methods to use molecular data available in The Cancer Genome Atlas to generate sample-specific models of cancer. Results By combining published models of different cells relevant to pancreatic ductal adenocarcinoma (PDAC), we built an agent-based model of the multicellular pancreatic tumor microenvironment, formally describing cell type–specific molecular interactions and cytokine-mediated cell-cell communications. We used an ensemble-based modeling approach to systematically explore how variations in the tumor microenvironment affect the viability of cancer cells. The results suggest that the autocrine loop involving EGF signaling is a key interaction modulator between pancreatic cancer and stellate cells. EGF is also found to be associated with previously described subtypes of PDAC. Moreover, the model allows a systematic exploration of the effect of possible therapeutic perturbations; our simulations suggest that reducing bFGF secretion by stellate cells will have, on average, a positive impact on cancer apoptosis. Conclusions The developed framework allows model-driven hypotheses to be generated regarding therapeutically relevant PDAC states with potential molecular and cellular drivers indicating specific intervention strategies.

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