Document Detail


Early stage hit triage for plant chemical genetic screens and target site identification.
MedLine Citation:
PMID:  24306874     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The increasing use of plant biological screens of large compound libraries to discover informative chemical probes for plant chemical genetics requires efficient methods for hit selection and advancement. Downstream target identification and validation studies with selected chemistries can also be resource-intensive and have a significant failure rate. Several steps and considerations for early stage hit triage are outlined to increase the probability of success that downstream studies with the chemical probe will be robust and productive, especially for target site discovery. Conversely, problematic compounds can be shelved or avoided entirely, saving time and resources. These steps include assessment of compound availability, purity, stability and solubility; determination of the biological dose-response; early and iterative evaluation of analogs; avoidance of promiscuous "frequent-hitters"; consideration of physicochemical parameters affecting compound bioavailability and mobility, use of "low-barrier" biological testing systems; and assessing the potential for compound metabolism or bioconversion.
Authors:
Terence A Walsh
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Methods in molecular biology (Clifton, N.J.)     Volume:  1056     ISSN:  1940-6029     ISO Abbreviation:  Methods Mol. Biol.     Publication Date:  2014  
Date Detail:
Created Date:  2013-12-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9214969     Medline TA:  Methods Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  191-9     Citation Subset:  IM    
Affiliation:
Discovery Research, Dow AgroSciences LLC, Indianapolis, IN, USA.
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