In vivo evaluation of indolyl glyoxamides in the phenotypic sea urchin embryo assay
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Marina N Semenova Alex S Kiselyov Ilia Y Titov Mikhail M Raihstat Maxim Molodtsov Ekaterina Grishchuk Ilia Spiridonov Victor V SemenovAbstract
We have devised a ?one-pot? phenotypic in vivo assay for the rapid evaluation of potential tubulin inhibitors using the sea urchin embryo model. An effect of a small molecule on two specific developmental stages of sea urchin embryo, namely: (i) fertilized egg test for antimitotic activity and (ii) behavioral monitoring of a free-swimming blastulae for changes in the embryo swimming pattern could be quantified by a threshold concentration resulting in respective abnormalities. Derivatives of the clinical candidate D-24851 featured good correlation between activity in tubulin polymerization assay and our in vivo data. Importantly, we demonstrated that in these series, the N-substitution of indole is non-essential to attain profound in vitro and cellular effects.
Journal details
Journal Chemical Biology & Drug Design
Volume 70
Issue number 6
Pages 485-490
Publication date
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Publisher website (DOI) 10.1111/j.1747-0285.2007.00591.x
Europe PubMed Central 17991295
Pubmed 17991295
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