Article
Biochemistry & Molecular Biology
Sang-Yun Lee, Lily M. Park, Yoo Jung Oh, Dong Hyuk Choi, Dong Woo Lee
Summary: The 3D cell migration assay was developed for evaluating drugs that inhibit cell migration. The assay overcomes the limitations of traditional methods by encapsulating cells in Matrigel on pillars and analyzing cell morphology. The micropillar/microwell chips allow simultaneous measurement of cell migration and viability, providing an effective method for drug evaluation.
Review
Oncology
Faris Alkhilaiwi
Summary: Cancer is a devastating disease with a low percentage of patients benefiting from genomics-based precision oncology. Functional diagnostics and patient-derived cancer models are needed for precision cancer therapy. The combination of conditional cell reprogramming and robotic high-throughput screening has the potential to drive precision cancer therapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemical Research Methods
Celine Rens, Tirosh Shapira, Sandra Pena-Diaz, Joseph D. Chao, Tom Pfeifer, Yossef Av-Gay
Summary: The authors developed AUTOptosis, a cost-effective and rapid apoptosis monitoring method based on quantifying nuclei intensity via staining with Hoechst 33342. They calibrated the method with standard apoptosis inducers in multiple cell lines, validated its applicability for high-content screening using a compound library, and demonstrated its specificity by detecting apoptosis triggered by Mycobacterium tuberculosis infections. AUTOptosis method involves morphological analysis of nuclear condensation during caspase-3-dependent apoptosis, where Hoechst-stained nuclei appear brighter during apoptosis and fade during necrosis, providing an apoptosis index for comparing test and control conditions.
Article
Biochemical Research Methods
Yuka Otsuka, Michael Airola, Yong-Mi Choi, Nicolas Coant, Justin Snider, Chris Cariello, Essa M. Saied, Christoph Arenz, Thomas Bannister, Ron Rahaim, Yusuf A. Hannun, Justin Shumate, Louis Scampavia, John D. Haley, Timothy P. Spicer
Summary: This study describes the development of inhibitors for human neutral ceramidase (nCDase) using a fluorescence-based enzyme activity method in a high-throughput screening format. Over 650,000 small molecules were screened, leading to the identification of several lead series of hits. Chemical optimization resulted in improved potency and selectivity over counterscreen assays, paving the way for further crystal docking studies and in vitro drug metabolism and pharmacokinetics (DMPK) research.
Article
Virology
Anushka Ramjag, Sergej Cutrone, Kai Lu, Christine Crasto, Jing Jin, Sonia Bakkour, Christine V. F. Carrington, Graham Simmons
Summary: This study describes a high-throughput method for screening inhibitors of alphavirus budding and identifies several antibodies with potent anti-budding activity. The findings provide important candidates for the development of therapeutics and prophylaxis against CHIKV and MAYV.
Article
Virology
Xiaojing Wen, Li Zhang, Qiang Liu, Xinyue Xiao, Weijin Huang, Youchun Wang
Summary: A high-throughput screening method was developed to identify compounds with inhibitory effects on Hantavirus. Cepharanthine, one of the identified compounds, showed promising activity in vitro and in vivo. These findings could potentially contribute to the treatment of Hantavirus infections.
Article
Biochemistry & Molecular Biology
Bastien Malbert, Virginie Labaurie, Cecile Dorme, Eric Paget
Summary: The search for new antifungal compounds in agriculture has focused on finding new modes of action, including new molecular targets such as coding and non-coding RNA. This study shows that group I introns in phytopathogenic fungi have self-splicing activity in vitro, which can be used in high-throughput screening to discover new antifungal compounds. The results suggest that group I introns may be selectively targeted by small molecules in future screenings, opening up possibilities for studying their druggability in crop pathogens.
Article
Biochemistry & Molecular Biology
Hyun Lee, Isoo Youn, Robel Demissie, Tasneem M. Vaid, Chun-Tao Che, Dimitri T. Azar, Kyu-Yeon Han
Summary: Matrix metalloproteinases (MMPs) play important roles in physiological and pathological processes. In this study, a fluorescence-based enzymatic assay and surface plasmon resonance were used to identify MMP-14 inhibitors. Clioquinol and chloroxine, both containing a quinoline structure, showed selective inhibitory activity against MMP-14.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yanli Sun, Haibo Lu, Xueyu Fang, Senhao Xiao, Feng Yang, Yantao Chen, Hongbo Wang, Xiaopeng Li, Jing Lu, Hua Lin, Cheng Luo, Kehao Zhao, Shijie Chen
Summary: Tumor suppressor p53-binding protein 1 (53BP1) plays a crucial role in DNA Damage Repair pathways and its dysregulation is associated with various diseases including cancer. Recent studies have identified a novel and effective 53BP1-TTD inhibitor DP308, disrupting the binding between 53BP1 and H4K20me2 peptide, showing promise as a potential tool for further optimization of biological functions and gene editing therapies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Nikunj M. Shukla, Fumi Sato-Kaneko, Shiyin Yao, Minya Pu, Michael Chan, Fitzgerald S. Lao, Yukiya Sako, Tetsuya Saito, Karen Messer, Tomoko Hayashi, Howard B. Cottam, Maripat Corr, Dennis A. Carson
Summary: Extracellular vesicles play a crucial role in intercellular communication and immune regulation. Researchers have identified small molecule compounds that can enhance the immunogenicity of vaccines by increasing the release of extracellular vesicles. The compounds were screened and validated through multiple assays, leading to the discovery of potential vaccine adjuvants.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katja F. Hellendahl, Maryke Fehlau, Sebastian Hans, Peter Neubauer, Anke Kurreck
Summary: The study introduces a luciferase-based assay for the detection of NK activity, which was validated in a 96-well plate format. The high-throughput assay showed comparable results to HPLC analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xu Zhang, Xuening Chen, Lian Lu, Qianqian Fang, Chun Liu, Zhonghui Lin
Summary: The MUS81-EME1/2 endonucleases are important for DNA replication and recombination, and are potential drug targets for enhancing the anti-cancer effects of DNA-damaging agents. In this study, a high-throughput screening identified dyngo-4a as a potent inhibitor of MUS81. Dyngo-4a effectively inhibited the endonuclease activities of both MUS81-EME1 and MUS81-EME2 complexes, and prevented them from binding to DNA substrates.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Toxicology
Isabel Ferreira, Goncalo Brites, Ana Silva, Francisco Caramelo, Barbara Oliveiros, Bruno Miguel Neves, Maria Teresa Cruz
Summary: Chemical-peptide conjugation is the molecular initiating event in skin sensitization, and has been used in the development of peptide reactivity assays. The ProtReact assay is a spectrophotometric method for measuring skin sensitization potential based on this event, and shows similar predictive capacities to the DPRA assay.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Srishyam Raghavan, Brian P. Chaplin, Shafigh Mehraeen
Summary: Predicting the adsorption energies of small molecules on electrocatalysts is important for accelerating design and screening. Descriptors based on geometric and electronic properties have limitations in predicting adsorption energies on different substrates. Machine learning algorithms CGCNN and ALIGNN outperform these descriptors in adsorption energy predictions.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Automation & Control Systems
Naiqi Wu, Yan Qiao, Zhiwu Li, Abdulrahman M. Al-Ahmari, Abdul-Aziz El-Tamimi, Husam Kaid
Summary: This article studies the scheduling problem of an HTS system for an enzymatic assay, a typical application of HTSs, from the perspective of control theory. The article presents a model using resource-oriented Petri nets (ROPNs) and establishes necessary and sufficient conditions for the existence of a feasible cyclic schedule. The article also determines the number of microplates needed for concurrent processing and the activity sequence for an optimal and feasible schedule, achieving a feasible and optimal cyclic schedule through simple computations.
IEEE TRANSACTIONS ON SYSTEMS MAN CYBERNETICS-SYSTEMS
(2022)