J Chem Inf Model - Characterizing the diversity and biological relevance of the MLPCN assay manifold and screening set.

Tópicos

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{ studi(1410) differ(1259) use(1210) }
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{ cost(1906) reduc(1198) effect(832) }
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{ method(2212) result(1239) propos(1039) }
{ detect(2391) sensit(1101) algorithm(908) }

Resumo

The NIH Molecular Libraries Initiative (MLI), launched in 2004 with initial goals of identifying chemical probes for characterizing gene function and druggability, has produced PubChem, a chemical genomics knowledgebase for fostering translation of basic research into new therapeutic strategies. This paper assesses progress toward these goals by evaluating MLI target novelty and propensity for undergoing biochemically or therapeutically relevant modulations and the degree of chemical diversity and biogenic bias inherent in the MLI screening set. Our analyses suggest that while MLI target selection has not yet been fully optimized for biochemical diversity, it covers biologically interesting pathway space that complements established drug targets. We find the MLI screening set to be chemically diverse and to have greater biogenic bias than comparable collections of commercially available compounds. Biogenic enhancements such as incorporation of more metabolite-like chemotypes are suggested.

Resumo Limpo

nih molecular librari initi mli launch initi goal identifi chemic probe character gene function druggabl produc pubchem chemic genom knowledgebas foster translat basic research new therapeut strategi paper assess progress toward goal evalu mli target novelti propens undergo biochem therapeut relev modul degre chemic divers biogen bias inher mli screen set analys suggest mli target select yet fulli optim biochem divers cover biolog interest pathway space complement establish drug target find mli screen set chemic divers greater biogen bias compar collect commerci avail compound biogen enhanc incorpor metabolitelik chemotyp suggest

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