Drug discovery targeted at transthyretin cardiac amyloidosis: rational design, synthesis, and biological activity of new transthyretin amyloid inhibitors

D. Blasi, M. Pinto, J. Nieto, G. Arsequell, G. Valencia, A. Planas, N. B. Centeno, J. Quintana

Producció científica: Article en revista indexadaArticle de conferènciaAvaluat per experts

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Resum

We have previously designed and synthesized ligands that stabilize the transthyretin (TTR) tetramer, in order to obtain therapeutically active compounds for familial amyloid polyneuropathy. We are hereby reporting a drug design strategy to optimize these ligands to target familial amyloid cardiomyopathy, through the following steps: (a) Structure Activity Relationship (SAR) analyses of the ligands described previously for the TTR tetramer, classified in structurally similar families; (b) drug design/optimization of TTR ligands through docking in the TTR tetramer three-dimensional structure and through optimization of physicochemical/pharmacokinetic/selectivity properties; (c) comparative structural analyses of selected amyloidogenic and non-amyloidogenic TTR mutants and native TTR structures; and (d) virtual screening of commercially available ligands and therapeutically active compounds (repurposing) towards wild-type and mutant TTR tetramer structures. First results in steps (a) and (d) of this strategy will be reported.

Idioma originalAnglès
Pàgines (de-a)55-57
Nombre de pàgines3
RevistaAmyloid
Volum18
NúmeroSuppl. 1
DOIs
Estat de la publicacióPublicada - de juny 2011
EsdevenimentInternational Symposium on Amyloidosis from Molecular Mechanisms Toward the Cure of Systemic Amyloidoses - Roma, Italy
Durada: 18 d’abr. 201021 d’abr. 2010
Número del congrés: 12th

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