Article
Agriculture, Multidisciplinary
Tokio Morita, Takeshi Akiyoshi, Toshiaki Tsuchitani, Hiroki Kataoka, Naoya Araki, Kodai Yajima, Kazuhiro Katayama, Ayuko Imaoka, Hisakazu Ohtani
Summary: This study found that cranberry juice inhibits the key proteins (OATP1A2 and OATP2B1) responsible for drug absorption in the intestines. The component avicularin in cranberry juice was identified as a novel inhibitor. Cranberry juice may interact with drugs that are substrates of OATPs.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Nutrition & Dietetics
Philip G. Kasprzyk, Larry Tremaine, Odette A. Fahmi, Jing-Ke Weng
Summary: This study examined the effects of bioengineered salidroside on various enzymes and drug transport proteins in the human body. The results showed that salidroside at normal plasma concentrations does not pose a risk for drug-drug interactions. It can be safely used in combination with other drugs that undergo similar metabolism or disposition pathways.
Article
Biochemistry & Molecular Biology
Orsolya Ungvari, Laura Kiraly, Eva Bakos, Csilla Ozvegy-Laczka
Summary: This study introduces a new fluorogenic indicator, Ace, which can enter cells through the function of OATP1B1/3 or OATP2B1, undergo conversion into highly fluorescent pyranine, allowing real-time assessment of hepatic OATP function and drug interactions without the need for washing. Additionally, Ace can be used in a competitive counterflow assay to distinguish between transported substrates and inhibitors of OATP1B1. These fluorescence-based methods pave the way for high-throughput screening of interactions between new molecular entities and OATPs.
Article
Biochemistry & Molecular Biology
Orsolya Ungvari, Eva Bakos, Daniella Kovacsics, Csilla Ozvegy-Laczka
Summary: Organic anion transporting polypeptides (OATPs) play important roles in the absorption, clearance, and blood-brain barrier penetration of drugs. Investigating the interactions between OATPs and drugs is crucial for drug development. This study developed a novel fluorescence-based assay to differentiate between substrates and non-transported inhibitors of OATPs, and identified a FDA-approved drug, pentamidine, as a unique substrate of OATP1A2.
Article
Biochemistry & Molecular Biology
George-Rafael Samantsidis, Melina Fotiadou, Savvas Tzavellas, Sven Geibel, Ralf Nauen, Luc Swevers, Shane Denecke, John Vontas
Summary: This study functionally characterized the putative ecdysone importer (EcI) in two major agricultural moth pests, cotton bollworm and fall armyworm. The research sheds light on the ecdysone uptake mechanisms across insect species and expands our knowledge of the physiological roles of OATPs in the transportation of endogenous substances.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ruhul Kayesh, Vishakha Tambe, Chao Xu, Wei Yue
Summary: Impaired transport activity of hepatic OATP1B1 and OATP1B3 due to drug-drug interactions (DDIs) often leads to increased systemic exposure to substrate drugs. This study aimed to assess the OATP1B1- and OATP1B3-mediated DDI potential of the calcium channel blocker nicardipine. The results showed that nicardipine has the potential to cause OATP1B1/3-mediated DDIs, and the consideration of optimal preincubation conditions is important when assessing these interactions in vitro.
Article
Biochemistry & Molecular Biology
Xiaohong Zhang, Stephen H. Wright
Summary: In this study, the turnover rates (TORs) of MATE1 and OCT2 proteins expressed in CHO cells were determined using a quantitative western blot method. The results showed that MATE1 and OCT2 proteins represented 25% and 24%, respectively, of the total expression on the cell surface. The calculated TOR values for MATE1 and OCT2 were consistent with values determined for other transporters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Muhammad Erfan Uddin, Zahra Talebi, Sijie Chen, Yan Jin, Alice A. Gibson, Anne M. Noonan, Xiaolin Cheng, Shuiying Hu, Alex Sparreboom
Summary: Research showed that many tyrosine kinase inhibitors (TKIs) strongly inhibit the function of renal transporter MATE1, potentially affecting the elimination of oxaliplatin, without increasing the risk of kidney injury.
Article
Pharmacology & Pharmacy
Louise Breuil, Nora Ziani, Sarah Leterrier, Gaelle Hugon, Fabien Caille, Viviane Bouilleret, Charles Truillet, Maud Goislard, Myriam El Biali, Martin Bauer, Oliver Langer, Sebastien Goutal, Nicolas Tournier
Summary: This study investigated the impact of CYP inducers and inhibitors on the brain and plasma kinetics of [C-11]metoclopramide using PET imaging. The results showed that CYP induction or inhibition had negligible effects on the plasma kinetics and metabolism of [C-11]metoclopramide, but ritonavir significantly increased brain penetration.
Editorial Material
Pharmacology & Pharmacy
Roberto A. Abbiati, M. Guillaume Wientjes, Jessie L. -S. Au
Summary: Mathematical modeling has been a key tool in pharmaceutical research for over 50 years, with an increasing emphasis on using models to enhance drug development efficiency and effectiveness. By linking different scales in models and utilizing literature data, mechanisms of drug interactions were elucidated, suggesting that modeling is valuable for hypothesis generation and experiment design to identify potential drug-drug interactions.
Article
Biochemistry & Molecular Biology
Tatsuya Kawasaki, Chisa Kaneko, Ryosuke Nakanishi, Yoshinori Moriyama, Tomohiro Nabekura
Summary: This study investigated the transport characteristics of amiloride by human MATE1 and found that MATE1 transported amiloride at an extracellular pH of 7.4, with saturated uptake and a bell-shaped pH profile. Additionally, the study discovered that pyrimethamine and fampridine exhibited strong inhibition on MATE1.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Eva Bakos, Csilla Temesszentandrasi-Ambrus, Csilla Ozvegy-Laczka, Zsuzsanna Gaborik, Balazs Sarkadi, Agnes Telbisz
Summary: Orally administered small molecules, such as Molnupiravir and Nirmatrelvir, have shown potential as efficient treatments for COVID-19 with moderate side effects. However, drug-drug and drug-transporter interactions need to be considered. This study focused on the interactions between these antiviral agents and key human transporters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Fangrui Xiu, Magdalena Rausch, Zhibo Gai, Shanshan Su, Shijun Wang, Michele Visentin
Summary: Tyrosine kinase inhibitors (TKIs) have made decisive contributions in revolutionizing cancer therapy by offering non-invasive and tolerable treatments for improved quality of life. However, the efficacy and durability of TKI therapy can vary due to factors such as cancer molecular features, drug resistance, pharmacokinetic alterations caused by genetic variants, and unwanted drug interactions. This article reviews the interactions between TKIs and organic cation transporters (OCTs) in vitro and in vivo, and discusses their potential clinical implications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Ziqiang Li, Shuang Tian, Zengguang Wu, Xueyan Xu, Lei Lei, Yanfen Li, Baohe Wang, Yuhong Huang
Summary: The study investigated the effects of Ginkgo biloba L. leaves extracts (EGB) and non-alcoholic fatty liver disease (NAFLD) on hepatocyte organic anion transporting polypeptide (Oatp)1b2, and assessed the pharmacokinetics of EGB active ingredients in NAFLD rats. The results showed that NAFLD and EGB can alter the activity of hepatic uptake transporter Oatp1b2 individually or in combination, which may impact the clinical administration of EGB or Oatp1b2 substrates.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Nisha Kwatra, Marilyn E. Morris
Summary: When ketamine is co-administered with GHB, it can significantly affect their toxicokinetics/toxicodynamics interactions. In this case, MCT inhibition and GABA(B) receptor antagonism can serve as potential treatment strategies for GHB overdose when it is co-ingested with ketamine.
Article
Immunology
Ladina Keller, Marta S. Palmeirim, Shaali M. Ame, Said M. Ali, Maxim Puchkov, Joerg Huwyler, Jan Hattendorf, Jennifer Keiser
CLINICAL INFECTIOUS DISEASES
(2020)
Article
Chemistry, Medicinal
Ilona Vollrath, Roman Mathaes, Ahmad S. Sediq, Dhananjay Jere, Susanne Jorg, Jorg Huwyler, Hanns-Christian Mahler
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Leonie Wagner-Hattler, Gabriela Quebatte, Jennifer Keiser, Joachim Schoelkopf, Christian M. Schlepuetz, Joerg Huwyler, Maxim Puchkov
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2020)
Article
Chemistry, Medicinal
Christina Haeuser, Pierre Goldbach, Joerg Huwyler, Wolfgang Friess, Andrea Allmendinger
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Biochemical Research Methods
Daniel Ehrsam, Sandro Sieber, Mouhssin Oufir, Fabiola Porta, Matthias Hamburger, Joerg Huwyler, Henriette E. Meyer Zu Schwabedissen
BIOCONJUGATE CHEMISTRY
(2020)
Article
Pharmacology & Pharmacy
Claudia Suenderhauf, Benjamin Berger, Maxim Puchkov, Yasmin Schmid, Sabine Mueller, Joerg Huwyler, Manuel Haschke, Stephan Kraehenbuehl, Urs Duthaler
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2020)
Review
Pharmacology & Pharmacy
Andreas Schittny, Jorg Huwyler, Maxim Puchkov
Review
Chemistry, Multidisciplinary
Joachim Schuster, Atanas Koulov, Hanns-Christian Mahler, Pascal Detampel, Joerg Huwyler, Satish Singh, Roman Mathaes
PHARMACEUTICAL RESEARCH
(2020)
Article
Pharmacology & Pharmacy
Maryam Farzan, Gabriela Quebatte, Katrin Strittmatter, Florentine Marianne Hilty, Joachim Schoelkopf, Joerg Huwyler, Maxim Puchkov
Article
Pediatrics
Leonie Wagner-Hattler, Klara Kiene, Julia Bielicki, Marc Pfister, Maxim Puchkov, Joerg Huwyler
Summary: The study evaluated the acceptability of a novel child-appropriate oral dispersible tablet formulation. The results showed high acceptability among parents and children, with smooth administration process and no distress observed in any of the children. The proposed child-friendly dosage form is expected to improve drug adherence in pediatric patients.
Article
Biochemistry & Molecular Biology
Laura Nicolle, Jens Casper, Melanie Willimann, Celine M. A. Journot, Pascal Detampel, Tomaz Einfalt, Hiu Man Grisch-Chan, Beat Thony, Sandrine Gerber-Lemaire, Jorg Huwyler
Summary: The study developed a novel chitosan-derivative, dCS-Suc-LPEI-14, showing promising biocompatibility, cytotoxicity, and transfection efficiency. Through in vitro and in vivo experiments, its potential for non-viral gene therapy was confirmed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Patrick Hauswirth, Philipp Graber, Katarzyna Buczak, Riccardo Vincenzo Mancuso, Susanne Heidi Schenk, Juerg P. F. Nueesch, Jorg Huwyler
Summary: Mutated NS1 variants, particularly the NS1-T585E single-amino acid mutant, showed potential oncotoxic effects in human hepatocellular carcinoma cell lines. Proteomics analysis revealed new interaction partners and signaling pathways of NS1, providing mechanistic explanations for its oncolytic effects.
Review
Pharmacology & Pharmacy
Klervi Golhen, Michael Buettcher, Jonas Kost, Joerg Huwyler, Marc Pfister
Summary: The majority of therapeutics currently available are not suitable for pediatric patients, thus there is a need to develop child-friendly dosage forms. This review discusses the challenges and opportunities in the development of such dosage forms, including taste masking, tablet size, dose flexibility, excipient safety, and acceptability. It also explores the example of orally dispersible tablets (ODTs) as a child-friendly drug delivery strategy, utilizing inorganic particulate drug carriers as multifunctional excipients to address unique medical needs in infants and children while maintaining a favorable excipient safety and acceptability profile in these vulnerable patient populations.
Article
Chemistry, Medicinal
Joachim Schuster, Atanas Koulov, Hanns-Christian Mahler, Susanne Joerg, Joerg Huwyler, Kai Schleicher, Pascal Detampel, Roman Mathaes
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Nanoscience & Nanotechnology
Mahsa Sedighi, Fereshteh Rahimi, Mohammad-Ali Shahbazi, Ali Hossein Rezayan, Helene Kettiger, Tomaz Einfalt, Joerg Huwyler, Dominik Witzigmann
ACS APPLIED BIO MATERIALS
(2020)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)