Article
Chemistry, Medicinal
Veronika Temml, Jakub Kollar, Theresa Schoenleitner, Anna Hoell, Daniela Schuster, Zsofia Kutil
Summary: Virtual screening followed by in vitro testing was used to discover novel active compounds for Glutamate carboxypeptidase II (GCPII) inhibition. By creating structure- and ligand-based pharmacophore models, virtual screening of a compound library led to the identification of six hits with moderate to high inhibitory potency against GCPII. The best virtual hit, a modified xanthene, showed an IC50 value of 353 +/- 24 nM. These findings demonstrate the applicability of pharmacophore-based modeling in the discovery of GCPII-specific inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Veronika Temml, Jakub Kollar, Theresa Schoenleitner, Anna Hoell, Daniela Schuster, Zsofia Kutil
Summary: In this study, structure- and ligand-based pharmacophore models were used for virtual screening of the SPECS compound library to discover novel GCPII-specific inhibitors. Six hits with moderate to high inhibitory potency were found, and the best virtual hit, a modified xanthene, inhibited GCPII with an IC50 value of 353 +/- 24 nM. This research demonstrates the applicability of pharmacophore-based modeling for the discovery of GCPII-specific inhibitors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Multidisciplinary Sciences
Anuradha Kumar, Somsundaram Chettiar, Brian S. Brown, Julie Early, Juliane Ollinger, Megan Files, Mai A. Bailey, Aaron Korkegian, Devon Dennison, Matthew McNeil, James Metz, Augustine Osuma, Michael Curtin, Aaron Kunzer, Gail Freiberg, Milan Bruncko, Dale Kempf, Tanya Parish
Summary: A high-throughput phenotypic screening of a diverse chemical library identified 24 chemotypes with anti-tubercular activity. Further exploration revealed that MmpL3 may serve as the target or mechanism of resistance for these compounds.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Jie Li, Yan Zhou, Guy Eelen, Qing-tong Zhou, Wen-bo Feng, Viktorija Labroska, Fen-fen Ma, Hui-ping Lu, Mieke Dewerchin, Peter Carmeliet, Ming-wei Wang, De-hua Yang
Summary: The growth of solid tumors relies on tumor vascularization and endothelial cells. Targeting the glycolytic activity of endothelial cells can normalize tumor vessels, reduce metastasis, and improve chemotherapy outcomes.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Xian Chen, Sudini Ranshaya Fernando, Yin-Lau Lee, William Shu-Biu Yeung, Ernest Hung-Yu Ng, Raymond Hang-Wun Li, Kai-Fai Lee
Summary: Current contraception methods mainly interfere with folliculogenesis, fertilization, and embryo implantation through physical or hormonal approaches. This study discovered that Nemadipine-A can effectively inhibit embryo implantation by suppressing specific molecules in the endometrium. This provides a potential novel non-hormonal compound for contraception.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Medve Laura, Gealageas Ronan, Lam Bao Vy, Guillaume Valentin, Castillo-Aguilera Omar, Camberlein Virgyl, Catherine Piveteau, Rosell Melissa, Fleau Charlotte, Warenghem Sandrine, Charton Julie, Dumont-Ryckembusch Julie, Bosc Damien, Leroux Florence, van Endert Peter, Deprez Benoit, Deprez-Poulain Rebecca
Summary: ERAP2 is an emerging pharmacological target in cancer immunotherapy and autoinflammatory disease control, and selective inhibitors and activators have been identified in this study, which could serve as useful starting points for further optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Valeria Marrocco, Tuan Tran, Siying Zhu, Seung Hyuk Choi, Ana M. Gamo, Sijia Li, Qiangwei Fu, Marta Diez Cunado, Jason Roland, Mitch Hull, Van Nguyen-Tran, Sean Joseph, Arnab K. Chatterjee, Nikki Rogers, Matthew S. Tremblay, Weijun Shen
Summary: The text discusses the unfolded protein response (UPR) and cellular stress mechanisms, and the identification of a small molecule through high-throughput screening that can modulate UPR and ER stress. This compound demonstrates potential therapeutic effects in in vivo disease models.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Chemistry, Medicinal
Tiziana Ginex, Urtzi Garaigorta, David Ramirez, Victoria Castro, Vanesa Nozal, Ines Maestro, Javier Garcia-Carceles, Nuria E. Campillo, Ana Martinez, Pablo Gastaminza, Carmen Gil
Summary: The unprecedented COVID-19 global emergency has led us to actively search for repurposable agents among FDA approved drugs to provide immediate treatment opportunities for patients. Through a hierarchical in silico/in vitro protocol, we successfully combined virtual and biological screening to expedite the identification of host-directed therapies against COVID-19.
Article
Biotechnology & Applied Microbiology
Jimin Tan, Nina Shenker-Tauris, Javier Rodriguez-Hernaez, Eric Wang, Theodore Sakellaropoulos, Francesco Boccalatte, Palaniraja Thandapani, Jane Skok, Iannis Aifantis, David Fenyo, Bo Xia, Aristotelis Tsirigos
Summary: Investigating how chromatin organization determines cell-type-specific gene expression is challenging. We present C.Origami, a deep neural network that predicts chromatin organization using DNA sequence and cell-type-specific genomic features. C.Origami enables in silico experiments to examine the impact of genetic changes on chromatin interactions. Applying this approach to leukemia cells and normal T cells, we discover novel chromatin regulation circuits in both normal and disease-related biological systems.
NATURE BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Edward Peter Booker, Ghassan E. Jabbour
Summary: Antiviral nanoparticles made from metal nanoparticles like gold, silver, and copper have the potential to kill or disable viruses that cause health problems in humans. This study used data mining to identify nanoparticle ligands for future antiviral nanoparticles, with nitric acid, phosphoroselenoic acid, hydroxyammonium, and pyrophosphoric acid showing promise. These findings will inform further experiments to accelerate the development of antiviral nanoparticles.
Article
Chemistry, Physical
Jungwoo Choi, Soonho Kwon, Youngtae Park, Ku Kang, Hyuck Mo Lee
Summary: The study revealed that EuAg5, BaAg5, and SrAg5 exhibit higher catalytic activities and durabilities than pure Ag, while LaAg5 and PrAg5 were proposed as promising new candidates. All candidates are characterized by containing alkaline earth metal or lanthanide elements in the space group P6/mmm.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Tunc Morova, Yi Ding, Chia-Chi F. Huang, Funda Sar, Tommer Schwarz, Claudia Giambartolomei, Sylvan C. Baca, Dennis Grishin, Faraz Hach, Alexander Gusev, Matthew L. Freedman, Bogdan Pasaniuc, Nathan A. Lack
Summary: The majority of disease-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) are located in non-coding regions. These variants can impact the binding of transcription factors to enhancer elements and alter gene expression. A high-throughput experimental method called snpSTARRseq was developed to functionally interrogate the activity of hundreds to thousands of non-coding variants on enhancer activity. Using this method, the researchers identified SNPs in prostate cancer risk-associated loci that significantly altered enhancer activity and provided a mechanism of action for certain GWAS risk regions.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Medicinal
Yiwei Zhang, Jiabei Guo, Jiongjia Cheng, Zhenghua Zhang, Fenghua Kang, Xiaoxing Wu, Qian Chu
Summary: Therapeutic peptides have revolutionized treatment for many human diseases. In recent decades, stapled helical peptides have made rapid progress in drug discovery. Compared to unstabilized linear peptides, stapled helical peptides have shown superior binding affinity, selectivity, membrane permeability, and metabolic stability, offering exciting potential for targeting challenging protein-protein interfaces. This Perspective summarizes the recent use of high-throughput screening technologies for identifying potent stapled helical peptides with optimized binding properties, aiming to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
S. M. Esther Rubavathy, Kandhan Palanisamy, S. Priyankha, Ramasamy Thilagavathi, Muthuramalingam Prakash, Chelliah Selvam
Summary: In this study, HDAC8 inhibitors with high affinity and good ADMET characteristics were screened from a natural product database. Through molecular docking, molecular dynamics, and MM-PBSA analysis, it was found that these compounds have strong binding affinity and are more effective than romidepsin. These findings may contribute to further development of HDAC8 inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Yuksel Cetin, Seyma Aydinlik, Aysen Gungor, Tugce Kan, Timucin Avsar, Serdar Durdagi
Summary: This review discusses various experimental techniques for COVID-19 research, including screening new drugs, developing antibodies, and interrupting infection/replication mechanisms. It provides accurate and relevant information on emerging technologies and helps researchers understand their strengths and limitations.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Daniel Spinks, Victoria Smith, Stephen Thompson, David A. Robinson, Torsten Luksch, Alasdair Smith, Leah S. Torrie, Stuart McElroy, Laste Stojanovski, Suzanne Norval, Iain T. Collie, Irene Hallyburton, Bhavya Rao, Stephen Brand, Ruth Brenk, Julie A. Frearson, Kevin D. Read, Paul G. Wyatt, Ian H. Gilbert
Article
Biochemistry & Molecular Biology
Maen Zeino, Ruth Brenk, Lisa Gruber, Martin Zehl, Ernst Urban, Brigitte Kopp, Thomas Efferth
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2015)
Article
Multidisciplinary Sciences
Aurijit Sarkar, Ruth Brenk
Review
Chemistry, Medicinal
Illimar Hugo Rekand, Ruth Brenk
FUTURE MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Tracy Bayliss, David A. Robinson, Victoria C. Smith, Stephen Brand, Stuart P. McElroy, Leah S. Torrie, Chido Mpamhanga, Suzanne Norval, Laste Stojanovski, Ruth Brenk, Julie K. Frearson, Kevin D. Read, Ian H. Gilbert, Paul G. Wyatt
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Justin R. Harrison, Stephen Brand, Victoria Smith, David A. Robinson, Stephen Thompson, Alasdair Smith, Kenneth Davies, Ngai Mok, Leah S. Torrie, Iain Collie, Irene Hallyburton, Suzanne Norval, Frederick R. C. Simeons, Laste Stojanovski, Julie A. Frearson, Ruth Brenk, Paul G. Wyatt, Ian H. Gilbert, Kevin D. Read
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Raphael Klein, Pasquale Linciano, Giuseppe Celenza, Pierangelo Bellio, Sofia Papaioannou, Jesus Blazquez, Laura Cendron, Ruth Brenk, Donatella Tondi
Article
Multidisciplinary Sciences
Lina Irsheid, Thomas Wehler, Christoph Borek, Werner Kiefer, Ruth Brenk, Maria Elena Ortiz-Soto, Juergen Seibel, Tanja Schirmeister
Article
Chemistry, Medicinal
Christian Kersten, Edmond Fleischer, Josef Kehrein, Christoph Borek, Elmar Jaenicke, Christoph Sotriffer, Ruth Brenk
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Raphael Klein, Laura Cendron, Martina Montanari, Pierangelo Bellio, Giuseppe Celenza, Lorenzo Maso, Donatella Tondi, Ruth Brenk
Review
Infectious Diseases
Vipul Panchal, Ruth Brenk
Summary: Riboswitches, located in the untranslated region of RNA, regulate gene expression and are potential antibacterial targets. Lead compounds against various riboswitches have been identified through different screening methods and structure design.
Review
Chemistry, Medicinal
Kasper P. Lundquist, Vipul Panchal, Charlotte H. Gotfredsen, Ruth Brenk, Mads H. Clausen
Summary: The rapid development in fragment-based drug discovery and medicinal targeting of RNA has opened up possibilities for combining technologies and methods in novel ways. This review discusses the use of fragment-based screening against RNA targets, including the latest screening and hit validation methods, and provides insights on future perspectives in this field.
Article
Chemistry, Medicinal
Ludvik Olai Espeland, Charis Georgiou, Raphael Klein, Hemalatha Bhukya, Bengt Erik Haug, Jarl Underhaug, Prathama S. Mainkar, Ruth Brenk
Summary: This work establishes the foundation for structure-based exploration of PaFabF, by setting up an experimental toolbox and validating hits obtained from virtual screening, successfully screening 6 compounds binding to the malonyl-binding site of FabF.
Article
Chemistry, Medicinal
Illimar Hugo Rekand, Ruth Brenk
Summary: DrugPred_RNA is a structure-based druggability predictor developed to identify druggable RNA binding sites. The method performed well in discriminating druggable from less druggable protein binding sites and can contribute to direct drug discovery efforts for RNA targets. This predictor is robust against conformational and sequence changes in the binding sites, enhancing confidence in its performance.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Oncology
Mohamed E. M. Saeed, Onnf Kadioglu, Ean-Jeong Seo, Henry Johannes Greten, Ruth Brenk, Thomas Efferth
ANTICANCER RESEARCH
(2015)