Rapid discovery and structure-activity relationships of pyrazolopyrimidines that potently suppress breast cancer cell growth via SRC kinase inhibition with exceptional selectivity over ABL kinase. Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae. Patterns of substrate affinity, competition, and degradation kinetics underlie biological activity of thalidomide analogs. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Identification of a primary target of thalidomide teratogenicity. Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds. Leveraging large-scale behavioral profiling in zebrafish to explore neuroactive polypharmacology. Combined zebrafish-yeast chemical-genetic screens reveal gene-copper-nutrition interactions that modulate melanocyte pigmentation. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Polypharmacology in precision oncology: current applications and future prospects. Structural and functional view of polypharmacology. Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies. A whole-animal platform to advance a clinical kinase inhibitor into new disease space. Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation. Small molecule developmental screens reveal the logic and timing of vertebrate development. Allosteric activators of protein phosphatase 2A display broad antitumor activity mediated by dephosphorylation of MYBL2. Zebrafish earn their drug discovery stripes. Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome.
PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury. ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor. Preclinical animal models for dravet syndrome: seizure phenotypes, comorbidities and drug screening. Towards a comprehensive catalog of zebrafish behavior 1.0 and beyond. Screening drugs for myocardial disease in vivo with zebrafish: an expert update. Rare genetic blood disease modeling in zebrafish. Zebrafish: an important tool for liver disease research. Zebrafish MITF-low melanoma subtype models reveal transcriptional subclusters and MITF-independent residual disease. The stress-like cancer cell state is a consistent component of tumorigenesis. Expanding the CRISPR toolbox in zebrafish for studying development and disease. Liu, K., Petree, C., Requena, T., Varshney, P. Zebrafish knock-ins swim into the mainstream. Zebrafish models of human disease: gaining insight into human disease at ZFIN. Zebrafish models in translational research: tipping the scales toward advancements in human health. The zebrafish reference genome sequence and its relationship to the human genome. Here, we discuss how zebrafish is an important model for drug discovery, the process of how these discoveries emerge and future opportunities for maximizing zebrafish potential in medical discoveries. Often, drugs and drug leads explored in zebrafish have an inter-organ mechanism of action and would otherwise not be identified through targeted screening approaches.
These features enable high-throughput and high-content phenotypic drug screening, repurposing of available drugs for personalized and compassionate use, and even the development of new drug classes. Zebrafish respond to small molecules and drug treatments at physiologically relevant dose ranges and, when combined with cell-specific or tissue-specific reporters and gene editing technologies, drug activity can be studied at single-cell resolution within the complexity of a whole animal, across tissues and over an extended timescale. Zebrafish are well established for their contribution to developmental biology and have now emerged as a powerful preclinical model for human disease, as their disease characteristics, aetiology and progression, and molecular mechanisms are clinically relevant and highly conserved. Numerous drug treatments that have recently entered the clinic or clinical trials have their genesis in zebrafish.
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