Review
Chemistry, Multidisciplinary
Jiang Hong Cai, Xuan Zhe Zhu, Peng Yue Guo, Peter Rose, Xiao Tong Liu, Xia Liu, Yi Zhun Zhu
Summary: Drug discovery is a challenging process with a high failure rate. Click chemistry and computer-aided drug design (CADD) have emerged as promising approaches for new drug development. This review summarizes the recent advancements in click and computational chemistry, including efficient synthesis of drug candidates, modification of natural products, targeted delivery systems, and computer-aided drug discovery for target identification and compound optimization. These advancements provide inspiration for novel drug development in the future.
FRONTIERS IN CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Abhishek Saha, Hiroaki Suga, Ashraf Brik
Summary: Chemical manipulation of naturally occurring peptides offers a convenient route for generating analogs to screen different therapeutic targets. mRNA display provides advantages in terms of library size and the recovery of selected polypeptide sequences.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Cleildo P. Santana, Brock A. Matter, Madhoosudan A. Patil, Armando Silva-Cunha, Uday B. Kompella
Summary: This study aimed to determine corneal permeability and uptake in rabbit, porcine, and bovine corneas for twenty-five drugs and relate these parameters to drug physicochemical properties and tissue thickness through quantitative structure permeability relationships (QSPRs). The results showed that drug permeability was generally higher in rabbit cornea and comparable between bovine and porcine corneas. Corneal uptake between species correlated with a slope close to 1, indicating generally similar drug uptake per unit weight of tissue. The study also identified drug characteristics such as lipophilicity, heteroatom ratio, hydrogen bond acceptors, and tissue thickness that influence drug permeability and uptake.
Article
Biochemical Research Methods
Yu-Liang Wang, Fan Wang, Xing-Xing Shi, Chen-Yang Jia, Feng-Xu Wu, Ge-Fei Hao, Guang-Fu Yang
Summary: Effective drug discovery is crucial for treating diseases, but is hindered by high costs and long cycles. The introduction of the QSAR method has enhanced efficiency in drug discovery, while the Cloud 3D-QSAR server provides a comprehensive solution by integrating various functions to facilitate the development of good QSAR models.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Chemistry, Multidisciplinary
Chong Lu, Shien Liu, Weihua Shi, Jun Yu, Zhou Zhou, Xiaoxiao Zhang, Xiaoli Lu, Faji Cai, Ning Xia, Yikai Wang
Summary: SECSE is a novel gene design platform that integrates artificial intelligence and deep learning to efficiently search and generate small molecules with potential drug activity.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Giuseppe Ermondi, Diego Garcia-Jimenez, Giulia Caron
Summary: The study utilized the PROTAC-DB database to gather information on PROTACs and building blocks, calculating 2D descriptors and using graphical tools to analyze and compare the chemical space. Results indicated that linkers have different properties than E3 ligands and warheads, and analysis of three PROTACs with varying permeability showed that the most permeable compounds exhibit different properties compared to bRo5 drugs. The study also discussed the relevance of physicochemical descriptors on degradation activity using the PROTACpedia database.
Article
Food Science & Technology
Gabriela Cristina Soares Rodrigues, Mayara dos Santos Maia, Andreza Barbosa Silva Cavalcanti, Renata Priscila Costa Barros, Luciana Scotti, Carlos L. Cespedes-Acuna, Eugene N. Muratov, Marcus Tullius Scotti
Summary: Pesticides are commonly used to control insects and pests, but the overuse can have negative effects, leading to the search for natural alternatives. This study aimed to identify natural products with insecticidal potential against specific pests, utilizing QSAR models and molecular docking to prioritize promising compounds.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Review
Pharmacology & Pharmacy
Jingbo Yang, Yiyang Cai, Kairui Zhao, Hongbo Xie, Xiujie Chen
Summary: This review provides a summary and classification of molecular fingerprints, emphasizing their significance in early drug research and development. It serves as a guide for selecting appropriate fingerprints for compounds in drug R&D.
DRUG DISCOVERY TODAY
(2022)
Article
Multidisciplinary Sciences
Wilmer Leal, Eugenio J. Llanos, Andres Bernal, Peter F. Stadler, Jurgen Jost, Guillermo Restrepo
Summary: The periodic system was already encoded in the chemical space before its formulation, and the development of the periodic table was influenced by chemical events and the emphasis on organic chemicals. The atomic weights in the 19th century also played a role in the formation of the periodic table.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Meng-Qi Liu, Tong Wang, Qin-Ling Wang, Jie Zhou, Bao-Rong Wang, Bing Zhang, Kun-Long Wang, Hao Zhu, Ying-Hua Zhang
Summary: This study focuses on the prediction and discovery of natural food-derived compounds with anti-anxiety effects using QSAR models and molecular docking. Three compounds, including quercetin, lithocholic acid, and ferulic acid, were found to alleviate anxiety by inhibiting the GABA-T enzyme.
Article
Chemistry, Physical
Nour-El-Houda Hammoudi, Widad Sobhi, Ayoub Attoui, Tarek Lemaoui, Alessandro Erto, Yacine Benguerba
Summary: This study aims to discover promising active compounds for the treatment of Alzheimer's disease by inhibiting Acetylcholinesterase and Butyrylcholinesterase enzymes, through the establishment of two robust QSAR models. The results show a good prediction capacity of the models, leading to the screening of potential compounds with higher biological activity. Further drug-likeness evaluation and reactivity study suggest that the newly designed candidate drugs have promising potential and should be experimentally investigated for AChE and BuChE enzyme inhibition.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Chemistry, Medicinal
Gergely Takacs, David Havasi, Mark Sandor, Zsolt Dohanics, Gyorgy T. Balogh, Robert Kiss
Summary: In this study, a Do-It-Yourself (DIY) combinatorial chemistry library containing over 14 million almost completely novel products was presented. The library was built from 1000 low-cost building blocks and demonstrated its applicability in various drug discovery approaches. The internally built DIY chemical library was found to provide a viable alternative to external virtual catalogs by offering access to a large number of low-cost and quickly accessible potential chemical starting points for drug discovery.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Darren R. Flower
Summary: The underperformance of the pharmaceutical discovery process is mainly due to profit-driven rather than society-driven search for new pharmaceutical products. Insufficient funding and lack of systematic approaches result in underuse of innovative methods and limitations of dominant methodologies. To fully capitalize on the potential of pharmaceutical intervention, a fundamental shift in attitude towards reliance on computational approaches and moving away from commercial imperatives is essential.
Article
Chemistry, Multidisciplinary
Norma Flores-Holguin, Joan S. Salas-Leiva, Erick J. Nunez-Vazquez, Dariel Tovar-Ramirez, Daniel Glossman-Mitnik
Summary: Marine toxins pose significant risks to marine ecosystems and human health. Understanding their structures and properties is crucial for mitigating risks and exploring their potential as therapeutic agents. This study compares four marine toxins, examining their reactivity properties and bioavailability. By investigating their similarities, valuable insights for new drug development can be gained. Exploring the lipophilic and hydrophilic properties in drug design is important for drug distribution and interaction. By elucidating shared molecular properties, this research aims to guide future drug discovery efforts and contribute to the field of molecular toxinology. The findings expand knowledge on toxins, deepen understanding of their bioactivities, and unlock new therapeutic possibilities.
FRONTIERS IN CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Valeria V. Kleandrova, M. Natalia D. S. Cordeiro, Alejandro Speck-Planche
Summary: Drug discovery is crucial in fighting against various diseases, and computational methods have played an important role in rationalizing the search for novel drugs. However, the current computational methods have limitations in tackling multi-genic diseases and drug resistance. Multi-tasking models for quantitative structure-biological effect relationships (mtk-QSBER) have emerged to overcome these limitations.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Health Care Sciences & Services
Jan L. Brozek, Carlos Canelo-Aybar, Elie A. Akl, James M. Bowen, John Bucher, Weihsueh A. Chiu, Mark Cronin, Benjamin Djulbegovic, Maicon Falavigna, Gordon H. Guyatt, Ami A. Gordon, Michele Hilton Boon, Raymond C. W. Hutubessy, Manuela A. Joore, Vittal Katikireddi, Judy LaKind, Miranda Langendam, Veena Manja, Kristen Magnuson, Alexander G. Mathioudakis, Joerg Meerpohl, Dominik Mertz, Roman Mezencev, Rebecca Morgan, Gian Paolo Morgano, Reem Mustafa, Martin O'Flaherty, Grace Patlewicz, John J. Riva, Margarita Posso, Andrew Rooney, Paul M. Schlosser, Lisa Schwartz, Ian Shemilt, Jean-Eric Tarride, Kristina A. Thayer, Katya Tsaioun, Luke Vale, John Wambaugh, Jessica Wignall, Ashley Williams, Feng Xie, Yuan Zhang, Holger J. Schunemann
Summary: This study presents a conceptual approach for evaluating the certainty of evidence from modeling studies using the GRADE method. The results indicate that the domains determining the certainty of evidence also apply to assessing evidence from models. A framework for selecting the best evidence from models and a summary of preferred terminology are proposed to facilitate communication between modeling and health care disciplines.
JOURNAL OF CLINICAL EPIDEMIOLOGY
(2021)
Article
Rheumatology
Alejandro Artacho, Sandrine Isaac, Renuka Nayak, Alejandra Flor-Duro, Margaret Alexander, Imhoi Koo, Julia Manasson, Philip B. Smith, Pamela Rosenthal, Yamen Homsi, Percio Gulko, Javier Pons, Leonor Puchades-Carrasco, Peter Izmirly, Andrew Patterson, Steven B. Abramson, Antonio Pineda-Lucena, Peter J. Turnbaugh, Carles Ubeda, Jose U. Scher
Summary: This study investigated the potential of the human gut microbiome in predicting methotrexate (MTX) efficacy in new-onset rheumatoid arthritis (RA) patients. The analysis revealed significant associations between gut bacterial taxa abundance and genes with future clinical response, as well as a microbiome-based model that predicted lack of response to MTX. Ex vivo experiments also suggested a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes, supporting the value of the gut microbiome as a potential prognostic tool and therapeutic target in RA.
ARTHRITIS & RHEUMATOLOGY
(2021)
Article
Oncology
Nuria Gomez-Cebrian, Ayelen Rojas-Benedicto, Arturo Albors-Vaquer, Beatriz Bellosillo, Carlos Besses, Joaquin Martinez-Lopez, Antonio Pineda-Lucena, Leonor Puchades-Carrasco
Summary: The diagnosis of myeloproliferative neoplasms (MPNs) is controversial due to limitations in reproducibility and subjectivity, along with common somatic mutations in driver genes. Metabolomics was utilized to characterize serum metabolic profiles of MPNs patients (PV and ET) compared to healthy controls (HC) and secondary thrombocytosis (ST). Significant metabolic differences were found between PV and ET patients compared to HC and ST, suggesting the potential of metabolomics for disease differentiation.
Article
Cell Biology
Ines Domingo-Orti, Ruben Lamas-Domingo, Andreea Ciudin, Cristina Hernandez, Jose Raul Herance, Martina Palomino-Schatzlein, Antonio Pineda-Lucena
Summary: Aging is a complex physiological process with crucial biochemical transformations. This study found metabolic alterations in red blood cells during aging, influenced by both obesity and age. The metabolomics profile of red blood cells was also impacted by obesity, sometimes mirroring and other times contrasting with the changes induced by aging.
Article
Chemistry, Medicinal
Obdulia Rabal, Edurne San Jose-Eneriz, Xabier Agirre, Juan Antonio Sanchez-Arias, Irene de Miguel, Raquel Ordonez, Leire Garate, Estibaliz Miranda, Elena Saez, Amaia Vilas-Zornoza, Antonio Pineda-Lucena, Ander Estella, Feifei Zhang, Wei Wu, Musheng Xu, Felipe Prosper, Julen Oyarzabal
Summary: The study reports a first-in-class series of quinoline-based analogues that simultaneously inhibit histone deacetylases, DNA methyltransferase-1, and lysine methyltransferase G9a. These multitarget epigenetic inhibitors show promising in vitro and in vivo antitumor efficacy against multiple myeloma.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Teresa Lozano, Noelia Casares, Celia Martil-Otal, Blanca Anega, Marta Gorraiz, Jonathan Parker, Marta Ruiz, Virginia Belsue, Antonio Pineda-Lucena, Julen Oyarzabal, Juan Jose Lasarte
Summary: The study demonstrates the potential therapeutic impact of using synthetic peptides to disrupt Foxp3 protein-protein interactions in affecting Treg cell functionality in cancer treatment.
Article
Multidisciplinary Sciences
Marta Garrido-Jareno, Leonor Puchades-Carrasco, Leticia Orti-Perez, Jose Miguel Sahuquillo-Arce, Maria del Carmen Meyer-Garcia, Joan Mollar-Maseres, Carmina Lloret-Sos, Ana Gil-Brusola, Jose Luis Lopez-Hontangas, Jose Manuel Beltran-Garrido, Javier Peman-Garcia, Antonio Pineda-Lucena
Summary: This study aims to evaluate the reliability of using SPR technology for quantifying anti-pneumococcal capsular polysaccharides (anti-PnPs) IgGs in vaccinated individuals.
SCIENTIFIC REPORTS
(2021)
Article
Allergy
Carolina Perales-Chorda, David Obeso, Laura Twomey, Ayelen Rojas-Benedicto, Leonor Puchades-Carrasco, Marta Roca, Antonio Pineda-Lucena, Jose Julio Laguna, Coral Barbas, Vanesa Esteban, Jaume Marti-Garrido, Ethel Ibanez-Echevarria, Ramon Lopez-Salgueiro, Domingo Barber, Alma Villasenor, Dolores Hernandez Fernandez de Rojas
Summary: This study aimed to explore metabolic changes in patients suffering from anaphylactic reactions based on triggers (food and/or drug) and severity (moderate and severe). Results indicate that different triggers or severity levels can induce differential metabolic changes at different time points, offering new insights into understanding, diagnosing, and treating anaphylaxis.
CLINICAL AND EXPERIMENTAL ALLERGY
(2021)
Article
Gastroenterology & Hepatology
Maria Garate-Rascon, Miriam Recalde, Maddalen Jimenez, Maria Elizalde, Maria Azkona, Iker Uriarte, M. Uxue Latasa, Raquel Urtasun, Idoia Bilbao, Bruno Sangro, Carmen Garcia-Ruiz, Jose C. Fernandez-Checa, Fernando J. Corrales, Argitxu Esquivel, Antonio Pineda-Lucena, Maite G. Fernandez-Barrena, Matias A. Avila, Maria Arechederra, Carmen Berasain
Summary: SLU7 plays a crucial role in maintaining hepatocellular identity and protecting against liver disease progression, by preserving the stability of HNF4 alpha 1 protein through its protective function against oxidative stress, thus preventing hepatocellular dedifferentiation.
Article
Biochemistry & Molecular Biology
R. Conde, R. Laires, L. G. Goncalves, A. Rizvi, C. Barroso, M. Villar, R. Macedo, M. J. Simoes, S. Gaddam, P. Lamosa, L. Puchades-Carrasco, A. Pineda-Lucena, A. B. Patel, S. C. Mande, S. Banerjee, M. Matzapetakis, A. Coelho
Summary: This study utilized Nuclear Magnetic Resonance based metabolomics to discover a signature of biomarkers for tuberculosis diagnosis. Six metabolites associated with TB infection were validated, in line with the recommendations of the World Health Organization.
BIOMEDICAL JOURNAL
(2022)
Article
Oncology
Borja Ruiz-Fernandez de Cordoba, Haritz Moreno, Karmele Valencia, Naiara Perurena, Pablo Ruedas, Thomas Walle, Alberto Pezonaga-Torres, Juan Hinojosa, Elisabet Guruceaga, Antonio Pineda-Lucena, Marta Abengozar-Muela, Denis Cochonneau, Carolina Zandueta, Susana Martinez-Canarias, Alvaro Teijeira, Daniel Ajona, Sergio Ortiz-Espinosa, Xabier Morales, Carlos Ortiz de Solorzano, Marta Santisteban, Luis Ramos-Garcia, Laura Guembe, Vratislav Strnad, Dominique Heymann, Sandra Hervas-Stubbs, Ruben Pio, Maria E. Rodriguez-Ruiz, Carlos E. de Andrea, Silvestre Vicent, Ignacio Melero, Fernando Lecanda, Rafael Martinez-Monge
Summary: Locoregional failure in breast cancer patients after surgery and irradiation is linked to a poor prognosis. The ENPP1/HP axis is exploited by tumor cells to promote local recurrence by suppressing immune cells. Blocking this axis offers new opportunities for therapeutic intervention.
Review
Oncology
Nuria Gomez-Cebrian, Jose Luis Poveda, Antonio Pineda-Lucena, Leonor Puchades-Carrasco
Summary: Prostate cancer is a heterogeneous tumor with a highly variable clinical outcome. Integrating multi-omics datasets can be a powerful approach for developing novel metabolic signatures to improve the clinical management of prostate cancer patients.
Article
Cell Biology
Cristina Solana-Manrique, Francisco Jose Sanz, Isabel Torregrosa, Martina Palomino-Schatzlein, Carolina Hernandez-Oliver, Antonio Pineda-Lucena, Nuria Paricio
Summary: The study investigates metabolic disturbances underlying the pathogenesis of Parkinson's disease (PD) using a Drosophila PD model. Through metabolomic analysis, the study finds that metabolic alterations are associated with PD and could potentially serve as therapeutic targets and biomarkers for the disease.
Review
Chemistry, Medicinal
Nuria Gomez-Cebrian, Pedro Vazquez Ferreiro, Francisco Javier Carrera Hueso, Jose Luis Poveda Andres, Leonor Puchades-Carrasco, Antonio Pineda-Lucena
Summary: Pharmacometabolomics studies focus on predicting individual responses and adverse reactions to drug treatments by analyzing metabolic profiles, which can guide patient selection in clinical trials to enhance drug efficacy and safety. This approach, closely linked to phenotype, provides valuable insights into specific metabolic changes associated with therapeutic interventions.
Review
Veterinary Sciences
Cathalijn Leenaars, Katya Tsaioun, Frans Stafleu, Kieron Rooney, Franck Meijboom, Merel Ritskes-Hoitinga, Andre Bleich
Summary: Before embarking on an animal research project, conducting a thorough literature review is essential to avoid redundancy, improve research reliability, and address research questions effectively. Understanding the various types of literature reviews and their associated terminology can help clarify conclusions and prevent ambiguity in research interpretation.
LABORATORY ANIMALS
(2021)
