Gene expression and cell morphology data are high-dimensional biological readouts of much recent interest for drug discovery. They are able to describe biological systems in different states (e.g., healthy and diseased), as well as biological systems before and after compound treatment, and they are hence useful for matching both spaces (e.g., for drug repurposing) as well as for characterizing compounds with respect to efficacy and safety endpoints. This Microperspective describes recent advances in this direction with a focus on applied drug discovery and drug repurposing, as well as outlining what else is needed to advance further, with a particular focus on better understanding the applicability domain of readouts and their relevance for decision making, which is currently often still unclear.
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http://dx.doi.org/10.1021/acsmedchemlett.3c00015 | DOI Listing |
NPJ Biofilms Microbiomes
January 2025
Institute of Drug Discovery Technology, Ningbo University, Ningbo, 315211, Zhejiang, China.
Dispersal plays a crucial role in the development and ecology of biofilms. While extensive studies focused on elucidating the molecular mechanisms governing this process, few have characterized the associated temporal changes in composition and structure. Here, we employed solid-state nuclear magnetic resonance (NMR) techniques to achieve time-resolved characterization of Bacillus subtilis biofilms over a 5-day period.
View Article and Find Full Text PDFAnal Chem
January 2025
School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China.
Formamidopyrimidine DNA glycosylase (Fpg) and flap endonuclease 1 (FEN1) are essential to sustaining genomic stability and integrity, while the abnormal activities of Fpg and FEN1 may lead to various diseases and cancers. The development of simple methods for simultaneously monitoring Fpg and FEN1 is highly desirable. Herein, we construct a multiple cyclic ligation-promoted exponential recombinase polymerase amplification (RPA) platform for sensitive and simultaneous monitoring of Fpg and FEN1 in cells and clinical tissues.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal, Academy of Higher Education, Manipal, Karnataka 576104, India.
Fragment-Based Drug Discovery (FBDD) has revolutionized drug discovery by overcoming the challenges of traditional methods like combinatorial chemistry and high-throughput screening (HTS). Leveraging small, low-molecular-weight fragments, FBDD achieves higher hit rates, reduced screening costs, and faster development timelines for clinically relevant drug candidates. This review explores FBDD's core principles, innovative methodologies, and its success in targeting diverse protein classes, including previously "undruggable" targets.
View Article and Find Full Text PDFJ Cheminform
January 2025
School of Systems Biomedical Science, Soongsil University, 369 Sangdo-ro, Dongjak-gu, 06978, Seoul, Republic of Korea.
G protein-coupled receptors (GPCRs) play vital roles in various physiological processes, making them attractive drug discovery targets. Meanwhile, deep learning techniques have revolutionized drug discovery by facilitating efficient tools for expediting the identification and optimization of ligands. However, existing models for the GPCRs often focus on single-target or a small subset of GPCRs or employ binary classification, constraining their applicability for high throughput virtual screening.
View Article and Find Full Text PDFJ Phys Chem A
January 2025
Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, The School of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350108, People's Republic of China.
The ligation strategy has been widely used in the chemical synthesis of atomically precise clusters. A series of thymine (T)-ligated Al-T ( = Be, Al, C; = 1-5) complexes have been studied to reveal the effect of DNA nucleobase ligands on the electronic structures of different superatoms in the present work. In addition to its protective role, the successive attachment of thymine ligands significantly lowers the adiabatic ionization energies (AIEs) of the studied Al superatoms with filled and unfilled electronic shells.
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