Article
Biochemistry & Molecular Biology
Blessy George, Xia Wen, Edgar A. Jaimes, Melanie S. Joy, Lauren M. Aleksunes
Summary: Research indicates that among five 5-HT3 antagonist drugs, ondansetron shows the strongest inhibitory effect on the OCT2 and MATE1 transporters, significantly impacting the transport of ASP(+) in cell experiments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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)
Review
Biochemistry & Molecular Biology
Kexin Lin, Xiaorui Kong, Xufeng Tao, Xiaohan Zhai, Linlin Lv, Deshi Dong, Shilei Yang, Yanna Zhu
Summary: This article reviews the traditional research methods of renal transporter-mediated drug-drug interactions (DDIs) and updates the recent progress in the development of methods. Through the sorting work conducted in this paper, it will be convenient for researchers at different learning stages to choose the best method for their own research based on their own subject's situation when they are going to study DDIs mediated by renal transporters.
Review
Chemistry, Medicinal
Marek Krzystanek, Stanislaw Surma, Artur Palasz, Monika Romanczyk, Krzysztof Krysta
Summary: The antidepressant effects of memantine in bipolar depression are promising, with both experimental and clinical evidence supporting its efficacy. The presented case study demonstrates that memantine can be an effective and safe adjunct treatment for mood stabilization in bipolar depression. This suggests that memantine may offer a new approach for patients who do not respond well to traditional medications.
Review
Pharmacology & Pharmacy
Abdulaziz Ahmed A. Saad, Fan Zhang, Eyad Abdulwhab H. Mohammed, Xin'an Wu
Summary: OCT2 and MATE1/2-K are crucial transporters in the kidneys that play a significant role in drug metabolism, therapeutic efficacy, and toxicity. Understanding the localization and functionality of these transporters is essential for preventing or enhancing drug-induced nephrotoxicity.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Chemistry, Analytical
Georgia Sidiropoulou, Abuzar Kabir, Kenneth G. Furton, Fotini S. Kika, Konstantinos Fytianos, Paraskevas D. Tzanavaras, Constantinos K. Zacharis
Summary: In this study, fabric phase sorptive extraction was successfully used for the rapid isolation of selected antiviral drugs from human urine. The optimized method showed high efficiency, speed, and promising clinical applications.
MICROCHEMICAL JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Pedro Caetano-Pinto, Simone H. Stahl
Summary: Organic anion transporters 1 and 3 (OAT1 and OAT3) are crucial for kidney function and play a role in regulating the secretion of small molecules and toxic by-products. Understanding the regulatory mechanisms of these transporters can aid in drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Materials Science, Multidisciplinary
Maedeh Kamel, Ebraheem Abdu Musad Saleh, Kamal Mohammadifard, Iroda Maratovna Nigmatova, Sheela Bijlwan, Montather F. Ramadan, J. M. Abbas Heshmati
Summary: In this study, the adsorption characteristics of pristine and doped (Si and Ge)-Al12N12 (AlN) and Al12P12 (AlP) nanocages towards the amantadine (AM) drug were investigated using density functional theory (DFT) in the gas phase. The results showed that the AM drug interacts with the hexagonal ring of AlN and AlP nanocages through its H atoms and -NH2 group. The adsorption energy of the doped AlN and AlP nanocages significantly increases towards the AM drug. The findings suggest that the doped AlN and AlP nanocarriers are efficient aspirants for the development of the AM drug delivery process.
MATERIALS CHEMISTRY AND PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Danuta Krasowska, Agnieszka Gerkowicz, Paula Wroblewska-Luczka, Aneta Grabarska, Katarzyna Zaluska-Ogryzek, Dorota Krasowska, Jarogniew J. Luszczki
Summary: Amantadine has anti-melanoma properties and can alleviate symptoms of Parkinson's disease. Amantadine combined with CDDP showed additive interaction in some melanoma cell lines, while its combination with MTO exhibited synergistic interaction in one cell line.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Naotoshi Yamamura, Tsuyoshi Mikkaichi, Ken-Ichi Itokawa, Misa Hoshi, Katja Damme, Stefanie Geigner, Christine Baumhauer
Summary: The aim of this study was to investigate the involvement of transporters in the renal secretion and absorption of mirogabalin. The results showed that mirogabalin is not a substrate of LAT1 but is associated with PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1, and/or MATE2-K.
Article
Chemistry, Multidisciplinary
Maya Chochkova, Almira Georgieva, Tsvetelina Ilieva, Madlena Andreeva, Georgi Pramatarov, Nejc Petek, Petranka Petrova, Martin Sticha, Yavor Mitrev, Jurij Svete
Summary: A series of cinnamic acid hybrids were synthesized and their antioxidant properties were evaluated. The hybrids containing a caffeoyl moiety and lipophilic adamantane core exhibited higher antioxidant activity, suggesting their potential benefits in pathological conditions associated with oxidative stress.
JOURNAL OF CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Pedro Caetano-Pinto, Nathanil Justian, Maria Dib, Jana Fischer, Maryna Somova, Martin Burchardt, Ingmar Wolff
Summary: The activity of drug transporters in the kidneys and their role in kidney cancer are still not well understood. In this study, different cell lines were used to investigate the activity, expression, and regulatory mechanisms of drug transporters in renal cell carcinoma (RCC). The results showed that RCC cells retained drug transport activity, with P-glycoprotein being localized in the nucleus. The pharmacological inhibition of P-glycoprotein enhanced cisplatin toxicity in non-malignant RPTECs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Shenjie Zhang, Haoqing Wu, Cynthia S. Day, Ulrich Bierbach
Summary: The study focused on platinum-acridine anticancer agents (PAs) with different linker moieties, including acyclic (1 and 3) and heterocyclic (R)-3-aminopiperidine (2) and 2-iminopyrrolidine (4). Rigidified 2 showed a positive correlation between potency and SLC47A1 gene expression levels in various cancer cell lines. The PAs displayed nanomolar activity in liver, lung, and breast cancer cells expressing high levels of SLC47A1, and were significantly more potent than cisplatin. The inhibition of MATE1 by PAs was observed in multiple cancer cell lines, suggesting that MATE1 could be a predictive marker and therapeutic target for PAs.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemical Research Methods
Manfred Schudok, Heiner Glombik, Volker Derdau
Summary: Two sodium-glucose cotransporter drug candidates, AVE2268 and AVE8887, show significant differences in synthesis, physiological and pharmacokinetic profiling despite their very similar chemical structures. This study highlights the importance of using radioactive compounds to study differences between closely related compounds before costly clinical trials.
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
(2021)
Article
Pharmacology & Pharmacy
Anne T. Nies, Joerg Koenig, Ute Hofmann, Charlotte Koelz, Martin F. Fromm, Matthias Schwab
Summary: Remdesivir has been approved for COVID-19 treatment, but the study indicates that OATP1B1 and its genetic variants, OATP1B3, OATP2B1 and OCT1, are not relevant for the hepatic uptake of the drug in humans. This suggests that there are no clinically relevant transporter-mediated drug interactions expected due to the rapid clearance of remdesivir.
Article
Chemistry, Medicinal
Katharina Halbach, Silke Aulhorn, Oliver Jens Lechtenfeld, Marion Lecluse, Sophia Leippe, Thorsten Reemtsma, Bettina Seiwert, Stephan Wagner, Joerg Koenig, Till Luckenbach
Summary: This study explored the interaction between bromoxynil and organic anion-transporting polypeptide zebrafish Oatp1d1, as well as the effect of BSP on the accumulation of bromoxynil and diclofenac in zebrafish embryos. The results indicate that Oatp1d1 plays an important role as an efflux transporter of ionic environmental compounds in zebrafish embryos.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Article
Pharmacology & Pharmacy
Fabian Mueller, Michael Sand, Glen Wunderlich, Jasmin Link, Christian Schultheis, Chantaratsamon Dansirikul, Rucha Sane, Roman Laszlo, Juergen M. Steinacker
Summary: The cardiac effects of BI 409306 in healthy volunteers during rest and exercise were evaluated in this study. The results showed that the changes in heart rate caused by BI 409306 were of low amplitude and transient, and were consistent with the pharmacokinetic profile of the drug.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Daniela B. Surrer, Martin F. Fromm, Renke Maas, Joerg Koenig
Summary: This study reveals an unknown link between NaCT/Nact transporter protein and L-arginine and its cardiovascular important derivatives, and demonstrates that arginine and its derivatives are substrates of NaCT/Nact. This finding is of significance for further investigation into the role of arginine and its derivatives in energy metabolism and brain development.
Article
Pharmacology & Pharmacy
Shingen Misaka, Yuko Ono, R. Verena Taudte, Eva Hoier, Hiroshi Ogata, Tomoyuki Ono, Jorg Konig, Hiroshi Watanabe, Martin F. Fromm, Kenju Shimomura
Summary: Green tea catechins can significantly reduce the exposure of fexofenadine, potentially by inhibiting intestinal absorption, but have no impact on the pharmacokinetics of pseudoephedrine.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Muhammad Erfan Uddin, Eric D. Eisenmann, Yang Li, Kevin M. Huang, Dominique A. Garrison, Zahra Talebi, Alice A. Gibson, Yan Jin, Mahesh Nepal, Ingrid M. Bonilla, Qiang Fu, Xinxin Sun, Alec Millar, Mikhail Tarasov, Christopher E. Jay, Xiaoming Cui, Heidi J. Einolf, Ryan M. Pelis, Sakima A. Smith, Przemyslaw B. Radwanski, Douglas H. Sweet, Joerg Koenig, Martin F. Fromm, Cynthia A. Carnes, Shuiying Hu, Alex Sparreboom
Summary: Dofetilide, a potassium current inhibitor used to prevent atrial fibrillation recurrence, can cause QTc interval prolongation and increase the risk of ventricular arrhythmias. This study identified MATE1 as a transporter for Dofetilide and showed that inhibiting or knocking out MATE1 resulted in increased retention of Dofetilide in cardiomyocytes and prolonged QTc interval in mice. The findings also explained the drug-drug interactions between Dofetilide and contraindicated drugs and were validated using a pharmacokinetic model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Grit Zahn, Diana M. Willmes, Nermeen N. El-Agroudy, Christopher Yarnold, Richard Jarjes-Pike, Sabine Schaertl, Kay Schreiter, Wiebke Gehrmann, Andrea Kuan Cie Wong, Tommaso Zordan, Joerg Koenig, Jens Jordan, Andreas L. Birkenfeld
Summary: This study evaluated the effects of a selective inhibitor ETG-5773 on liver steatosis and body fat accumulation in a mouse model. The results showed that ETG-5773 blocked citrate uptake mediated by mouse and human NaCT, reducing liver steatosis and body fat accumulation, and improving glucose regulation.
Article
Pharmacology & Pharmacy
Melanie Then, Thomas Tuemena, Anna Sledziewska, Karl-Guenter Gassmann, Renke Maas, Martin F. Fromm
Summary: Regulatory authorities place significant importance on the potential of new drugs to prolong the QT interval. The study analyzed prescriptions and co-prescriptions of QT drugs in a large elderly inpatient cohort to assess the development of QT drug burden. The findings revealed an increase in contraindicated co-prescriptions and the number of QT drugs per patient over the years. Regular updates of the CredibleMeds QT drugs list could help prevent medication errors related to QT drugs.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Fabian Mueller, Kathrin Hohl, Sascha Keller, Sven Schmidt-Gerets, Birgit Deutsch, Annette Schuler-Metz, Martin F. Fromm, Peter Stopfer, Arne Gessner
Summary: N-1-methylnicotinamide (NMN) is proposed as an endogenous biomarker for drug-drug interactions in the renal proximal tubule. NMN kinetics were analyzed in plasma and urine samples from two clinical trials involving a probe drug cocktail. The results showed that NMN clearance was specifically and sensitively affected by the inhibition of renal MATEs, indicating that NMNCLR can be used as a marker for MATE-mediated renal drug-drug interactions.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Georg Sebastian Hoenes, Ramona Gowry Sivakumar, Christoph Hoppe, Joerg Koenig, Dagmar Fuehrer, Lars Christian Moeller
Summary: MGL-3196 is a new thyromimetic agent that activates TR beta with high efficacy through specific transport by OATP1B1, leading to its hepatic thyromimetic action.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Bastian Haberkorn, Dennis Loewen, Lukas Meier, Martin F. F. Fromm, Joerg Koenig
Summary: Due to alternative splicing, the SLCO1B3 gene encodes two protein variants, Lt-OATP1B3 and Ct-OATP1B3, expressed in different tissues. The transcriptional regulation and transcription factors controlling the expression of these variants are not well understood. In this study, we cloned DNA fragments from the promoter regions of the Lt-SLCO1B3 and Ct-SLCO1B3 genes and investigated their activity in different cell lines. We identified potential binding sites for transcription factors and found that ZKSCAN3 and SOX9 are important for the cell type-specific regulation of the Ct-SLCO1B3 gene.
Article
Pharmacology & Pharmacy
Arne Gessner, Fabian Mueller, Pia Wenisch, Markus R. R. Heinrich, Joerg Koenig, Peter Stopfer, Martin F. F. Fromm
Summary: This study examines the sensitivity and specificity of endogenous biomarkers as tools for detecting drug-drug interactions mediated by renal transport proteins. Choline and trimethylamine N-oxide are identified as sensitive and specific biomarkers for OCT2/MATEs, while indoleacetyl glutamine and indoleacetic acid are found to be sensitive and specific biomarkers for renal OATs.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Chemistry, Medicinal
Fabian Grassl, Leonard Bock, Alvaro Huete-Huerta Gonzalez, Martin Schiller, Peter Gmeiner, Joerg Koenig, Martin F. Fromm, Harald Huebner, Markus R. Heinrich
Summary: Based on APH199, two novel groups of D-4 subtype selective ligands were designed and evaluated, showing bias toward G(i) signaling pathway over β-arrestin recruitment compared to quinpirole. These compounds exhibited different bias profiles in terms of efficacy, potency, and GRK2 dependency, ranging from 1 to over 300 bias factors and activation from 15% to over 98% compared to quinpirole. Docking studies provided insights into the role of ECL2 and EPB in bias emergence, utilizing the diversity of functionally selective D-4 agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)