In the past two decades, zebrafish genetic screens have identified a wealth of mutations that have been essential to the understanding of development and disease biology. More recently, chemical screens in zebrafish have identified small molecules that can modulate specific developmental and behavioural processes. Zebrafish are a unique vertebrate system in which to study chemical genetic systems, identify drug leads, and explore new applications for known drugs. Here, we discuss some of the advantages of using zebrafish in chemical biology, and describe some important and creative examples of small molecule screening, drug discovery and target identification.
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http://dx.doi.org/10.1186/1478-811X-8-11 | DOI Listing |
J Mol Histol
December 2024
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, P.O.Box 16635-148, Tehran, Iran.
Embryonic development during the preimplantation stages is highly sensitive and critically dependent on the reception of signaling cues. The precise coordination of diverse pathways and signaling factors is essential for successful embryonic progression. Even minor disruptions in these factors can result in physiological dysfunction, fetal malformations, or embryonic arrest.
View Article and Find Full Text PDFJ Med Chem
December 2024
Institute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Members of the casein kinase 1 (CK1) family have emerged as key regulators of cellular signaling and as potential drug targets. Functional annotation of the 7 human isoforms would benefit from isoform-selective inhibitors, allowing studies on the role of these enzymes in normal physiology and disease pathogenesis. However, due to significant sequence homology within the catalytic domain, isoform selectivity is difficult to achieve with conventional small molecules.
View Article and Find Full Text PDFElife
December 2024
Department of Neurology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Identifying target proteins for bioactive molecules is essential for understanding their mechanisms, developing improved derivatives, and minimizing off-target effects. Despite advances in target identification (target-ID) technologies, significant challenges remain, impeding drug development. Most target-ID methods use cell lysates, but maintaining an intact cellular context is vital for capturing specific drug-protein interactions, such as those with transient protein complexes and membrane-associated proteins.
View Article and Find Full Text PDFTrop Med Infect Dis
November 2024
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Tuberculosis (TB) is a global health challenge associated with considerable levels of illness and mortality worldwide. The development of innovative therapeutic strategies is crucial to combat the rise of drug-resistant TB strains. DNA Gyrase A (GyrA) and serine/threonine protein kinase (PknB) are promising targets for new TB medications.
View Article and Find Full Text PDFToxins (Basel)
December 2024
Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, 08036 Barcelona, Spain.
Pain is a frequent and disturbing symptom among hemodialysis patients. Protein-bound uremic toxins (PBUTs) are related to cardiovascular and overall mortality, and they are difficult to remove with current hemodialysis treatments. The PBUT displacers, such as furosemide, tryptophan, or ibuprofen, may be promising new strategies for improving their clearance.
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