Review
Chemistry, Medicinal
Tyler C. Beck, Kyle R. Beck, Jordan Morningstar, Menny M. Benjamin, Russell A. Norris
Summary: Adverse drug interactions account for roughly 2.8% of annual hospitalizations in the United States, with efforts to reduce these interactions often facing challenges in optimizing therapeutic outcomes. Preclinical drug design should consider cytochrome interactions to prevent development failures, but physiochemical and structural properties alone are insufficient to predict cytochrome inhibition accurately. Machine learning approaches offer a more robust and accurate way of predicting CYP inhibition.
Article
Chemistry, Medicinal
Sohvi Luukkonen, Erik Meijer, Giovanni A. Tricarico, Johan Hofmans, Pieter F. W. Stouten, Gerard J. P. van Westen, Eelke B. Lenselink
Summary: Protein kinases are a protein family with important roles in complex diseases. They have ATP binding sites that can be targeted to create multitarget drugs. Multitask deep learning models outperform single-task deep learning and tree-based models for protein kinase activity prediction.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Pharmacology & Pharmacy
Chiara Jeiziner, Celine K. Stauble, Markus L. Lampert, Kurt E. Hersberger, Henriette E. Meyer zu Schwabedissen
Summary: Pharmacogenotyping plays a crucial role in determining a patient's genetic susceptibility and providing genotype-driven treatment recommendations for medication efficacy and treatment plans. The complexity of integrating a patient's pharmacogenetic profile into treatment recommendations highlights the importance of considering genetic factors in personalized medicine.
PHARMACOGENOMICS & PERSONALIZED MEDICINE
(2021)
Article
Engineering, Environmental
Hang Yu, Meiqi Song, Keqi Hu, Yujian Wang, Ruifang Fan, Zongying Yang, Hansruedi Glatt, Albert Braeuning, Yungang Liu
Summary: Bisphenol compounds may increase the genotoxic effects of metabolically activated carcinogens by modulating the expression of nuclear receptors and xenobiotic-metabolizing enzymes in human liver cancer cells, potentially aggravating chromosome damage caused by impactful carcinogens in human cells.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alex R. Medeiros, Leonardo L. G. Ferreira, Mariana L. de Souza, Celso de Oliveira Rezende Junior, Rocio Marisol Espinoza-Chavez, Luiz Carlos Dias, Adriano D. Andricopulo
Summary: The study explored the design of cruzain inhibitors based on imidazole scaffolds through molecular docking and quantitative structure-activity relationship analysis. Models were built and key structural properties determining cruzain inhibition were identified, revealing novel insights for the design of improved inhibitors.
Article
Agriculture, Multidisciplinary
Juan Shi, Li-Xia Zhao, Jia-Yu Wang, Hai-Feng Cao, Shuang Gao, Fei Ye, Ying Fu
Summary: In this study, five compounds were obtained through multiple quantitative structure-activity relationship screening. Molecular docking and MD experiments showed that the constructed approach had good screening ability for HPPD inhibitors. This work provided molecular structural information for developing novel, highly efficient and low-toxicity HPPD inhibitors.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Biochemistry & Molecular Biology
Avinash Kumar, Sudhanshu Rai, Ekta Rathi, Paridhi Agarwal, Suvarna G. Kini
Summary: The study presents a pharmacophore-guided fragment-based design strategy for developing novel mTOR inhibitors. Designed molecules showed good binding affinity at both sites, with one molecule identified to have the highest predicted activity. The report introduces five potential mTOR dual inhibitors based on predicted activity and drug-likeness analysis.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Pharmacology & Pharmacy
Ante Milicevic, Goran Sinko
Summary: A QSAR regression model was developed to estimate the potency of compounds in inhibiting AChE activity, based on three simple descriptors. The model demonstrated stability and strong predictive power for different compounds. Its predictive ability was validated by accurately predicting pK(i) values of randomly selected compounds.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Lu Huang, Xulong Wu, Xiaoli Fu, Haoxiang Wang, Biao Tang, Yirong Xiao, Caixia Zhou, Zhiqiao Zhao, Yujun Wan, Hui Chen, Zizhong Tang, Huipeng Yao, Zhi Shan, Tongliang Bu
Summary: In this study, a combination of structure-based drug carriers and molecular docking-based virtual screening was used to screen new potential FGFR1 inhibitors, providing a new approach for further research to explore better therapeutic effects in cancer treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Vaishnav Bhaskar, Sunil Kumar, Aathira Sujathan Nair, S. Gokul, Prayaga Rajappan Krishnendu, Sonu Benny, C. T. Amrutha, Deepthi S. Manisha, Vaishnavi Bhaskar, Subin Mary Zachariah, T. P. Aneesh, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Leena K. Pappachen, Orazio Nicolotti, Bijo Mathew
Summary: In this study, an atom-based 3D QSAR model was developed to screen potential candidates for the treatment of drug-resistant tuberculosis. Through molecular docking, ADME profiling, and molecular dynamic simulations, the lead molecule ZINC11536150 was found to exhibit strong antibacterial activity and stability.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Pharmacology & Pharmacy
Maaike van der Lee, Henk-Jan Guchelaar, Jesse J. Swen
Summary: Genetic variants in the gene encoding CYP2D6 show substrate-specific effects in drug metabolism, with the CYP2D6*17 allele having higher debrisoquine clearance and the CYP2D6*10 allele having lower dextromethorphan clearance. However, more studies are needed due to sparse data on most substrates.
Review
Medicine, Research & Experimental
Fitri Fareez Ramli
Summary: Methadone has variable pharmacokinetics among individuals, and pharmacogenomic biomarkers show promise for personalized treatment. Certain genotypes and haplotypes can predict lower or higher methadone dose requirements.
BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES
(2021)
Review
Chemistry, Medicinal
Vaishali M. Patil, Neeraj Masand, Satya P. Gupta, Brian S. J. Blagg
Summary: Research on HSP90 as a promising target for anticancer drug development has shown that heterocyclic chemical moieties with HSP90 inhibitory activity have been successfully used by medicinal chemists to design novel drugs. Structure-activity relationship studies and QSAR models have been applied to assist the drug development process, providing insights into the core template required to design potent HSP90 inhibitors for anticancer agents.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ante Milicevic, Goran Sinko
Summary: This study developed QSAR models based on simple descriptors to estimate BChE inhibition potency of different compounds, achieving good correlation with certain topological and constitutional descriptors.
Article
Chemistry, Medicinal
Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar, Gopichand Gutti, Pravin Gore, Bharat Sahu, Ashok Kumar, Sushil Kumar Singh
Summary: This study successfully designed and synthesized effective BChE inhibitors through machine learning, and their activity was verified through in silico and in vitro evaluations.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Environmental Sciences
Anoop Kumar Sharma, Julie Boberg, Marianne Dybdahl
TOXICOLOGICAL AND ENVIRONMENTAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Kyrylo Klimenko, Sine A. Rosenberg, Marianne Dybdahl, Eva B. Wedebye, Nikolai G. Nikolov
Article
Environmental Sciences
Kamel Mansouri, Nicole Kleinstreuer, Ahmed M. Abdelaziz, Domenico Alberga, Vinicius M. Alves, Patrik L. Andersson, Carolina H. Andrade, Fang Bai, Ilya Balabin, Davide Ballabio, Emilio Benfenati, Barun Bhhatarai, Scott Boyer, Jingwen Chen, Viviana Consonni, Sherif Farag, Denis Fourches, Alfonso T. Garcia-Sosa, Paola Gramatica, Francesca Grisoni, Chris M. Grulke, Huixiao Hong, Dragos Horvath, Xin Hu, Ruili Huang, Nina Jeliazkova, Jiazhong Li, Xuehua Li, Huanxiang Liu, Serena Manganelli, Giuseppe F. Mangiatordi, Uko Maran, Gilles Marcou, Todd Martin, Eugene Muratov, Dac-Trung Nguyen, Orazio Nicolotti, Nikolai G. Nikolov, Ulf Norinder, Ester Papa, Michel Petitjean, Geven Piir, Pavel Pogodin, Vladimir Poroikov, Xianliang Qiao, Ann M. Richard, Alessandra Roncaglioni, Patricia Ruiz, Chetan Rupakheti, Sugunadevi Sakkiah, Alessandro Sangion, Karl-Werner Schramm, Chandrabose Selvaraj, Imran Shah, Sulev Sild, Lixia Sun, Olivier Taboureau, Yun Tang, Igor Tetko, Roberto Todeschini, Weida Tong, Daniela Trisciuzzi, Alexander Tropsha, George Van Den Driessche, Alexandre Varnek, Zhongyu Wang, Eva B. Wedebye, Antony J. Williams, Hongbin Xie, Alexey Zakharov, Ziye Zheng, Richard S. Judson
ENVIRONMENTAL HEALTH PERSPECTIVES
(2020)
Article
Biochemistry & Molecular Biology
Majorie B. M. van Duursen, Julie Boberg, Sofie Christiansen, Lisa Connolly, Pauliina Damdimopoulou, Panagiotis Filis, Paul A. Fowler, Bart M. Gadella, Jan Holte, Kersti Jaager, Hanna K. L. Johansson, Tianyi Li, Severine Mazaud-Guittot, Anne-Simone Parent, Andres Salumets, Ana M. Soto, Terje Svingen, Agne Velthut-Meikas, Eva Bay Wedebye, Yuling Xie, Martin van den Berg
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Andreas Kortenkamp, Marta Axelstad, Asma H. Baig, Ake Bergman, Carl-Gustaf Bornehag, Peter Cenijn, Sofie Christiansen, Barbara Demeneix, Arash Derakhshan, Jean-Baptiste Fini, Caroline Fraedrich, Timo Hamers, Lina Hellwig, Josef Koehrle, Tim I. M. Korevaar, Johan Lindberg, Olwenn Martin, Marcel E. Meima, Philipp Mergenthaler, Nikolai Nikolov, David Du Pasquier, Robin P. Peeters, Bjorn Platzack, Louise Ramhoj, Sylvie Remaud, Kostja Renko, Martin Scholze, Harald Stachelscheid, Terje Svingen, Fabian Wagenaars, Eva Bay Wedebye, R. Thomas Zoeller
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Environmental Sciences
Anna Kjerstine Rosenmai, Sofia Boeg Winge, Morlin Moller, Johan Lundqvist, Eva Bay Wedebye, Nikolai Georgiev Nikolov, Hanna Katarina Lilith Johansson, Anne Marie Vinggaard
Summary: The study screened OPFRs for their potential endocrine disruptive effects, finding that multiple OPFRs affected hormone receptors and other endocrine-related activities, warranting further research for risk assessment.
Article
Pharmacology & Pharmacy
Jorid B. Sorli, Marie Frederiksen, Nikolai G. Nikolov, Eva B. Wedebye, Niels Hadrup
Summary: This study investigated the potential carcinogenicity of spray-formulated engine/brake cleaners and lubricating agents sold in the European Union. It identified several substances with carcinogenic potential and suggests that regulators and manufacturers can use this information to reduce occupational risks.
Meeting Abstract
Toxicology
J. B. Sorli, M. Frederiksen, N. Nikolov, E. B. Wedebye, N. Hadrup
TOXICOLOGY LETTERS
(2022)
Meeting Abstract
Toxicology
J. Ardenkjaer-Skinnerup, A. C. V. E. Nissen, N. G. Nikolov, E. B. Wedebye, G. Ravn-Haren, N. Hadrup, U. Vogel
TOXICOLOGY LETTERS
(2022)
Article
Environmental Sciences
Nikolai G. Nikolov, Ana C. V. E. Nissen, Eva B. Wedebye
Summary: Large screening programs like US Tox21 are sharing in vitro experimental results for various endpoints related to human health. To ensure accurate (Q)SAR modelling, it is crucial to clearly define the endpoint and extract the most reliable data points. This study presents a comprehensive data curation procedure for interpreting in vitro experimental data sets, including selecting actives based on curve fitting quality, activity magnitude, and potency cut-offs, as well as considering factors like non-cytotoxicity and assay signal interference.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2023)
Review
Toxicology
Louise Ramhoj, Marta Axelstad, Yoni Baert, Ana I. Canas-Portilla, Frederic Chalmel, Lars Dahmen, Antonio De La Vieja, Bertrand Evrard, Ann-Cathrin Haigis, Timo Hamers, Kim Heikamp, Henrik Holbech, Patricia Iglesias-Hernandez, Dries Knapen, Lorna Marchandise, Jane E. Morthorst, Nikolai Georgiev Nikolov, Ana C. V. E. Nissen, Michael Oelgeschlaeger, Kostja Renko, Vera Rogiers, Gerrit Schueuermann, Evelyn Stinckens, Mette H. Stub, Monica Torres-Ruiz, Majorie Van Duursen, Tamara Vanhaecke, Lucia Vergauwen, Eva Bay Wedebye, Terje Svingen
Summary: Current test strategies for identifying thyroid hormone (TH) system disruptors are insufficient for robust chemical risk assessment, and alternative test methods are needed to infer a causal relationship between initial chemical disruption and adverse outcomes. This project aims to develop specific new approaches to TH system disruption by characterizing in vivo mechanisms of action and incorporating non-mammalian vertebrate test species alongside traditional laboratory rat species and human-derived in vitro assays.
FRONTIERS IN TOXICOLOGY
(2023)
Meeting Abstract
Toxicology
E. B. Wedebye, N. G. Nikolov
TOXICOLOGY LETTERS
(2021)
Article
Toxicology
Marianne Dybdahl, David Benjamin Selesko, Ulla Ramer Mikkelsen
Summary: The safety of Lacprodan (R) BLG was evaluated for genotoxicity and subchronic toxicity, showing no mutagenic potential in bacterial reverse mutation assay or clastogenic or aneugenic potential in an in vitro micronucleus assay. In a 90-day subchronic toxicity study on Wistar rats, no treatment-related adverse effects were observed at dose levels up to 1000 mg/kg bw/day, establishing the NOAEL for Lacprodan (R) BLG.
TOXICOLOGY REPORTS
(2021)