2024-03-29T07:01:20Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/495812012-05-13T22:00:00Zcom_10261_5063com_10261_5col_10261_5069
Retrospective Mapping of SAR Data for TTR Protein in Chemico-Biological Space Using Ligand Efficiency Indices as a Guide to Drug Discovery Strategies
Blasi, Daniel
Arsequell, Gemma
Valencia Parera, Gregorio
Nieto, Joan
Planas, Antoni
Pinto, Marta
Centeno, Nuria B.
Abad-Zapatero, Cele
Quintana, Jordi
TTR
Amyloid
Ligand efficiency indices
Chemico-biological space
We have previously reported the design and synthesis of ligands that stabilize Transthyretin protein (TTR) in order to obtain therapeutically active compounds for Familial Amyloid Polyneuropathy (FAP). We are hereby reporting a drug design strategy to optimize these ligands and map them in Chemico-Biological Space (CBS) using Ligand Efficiency Indices (LEIs). We use a binding efficiency index (BEI) based on the measured binding affinity related to the molecular weight (MW) of the compound combined with surface-binding efficiency index (SEI) based on Polar Surface Area (PSA). We will illustrate the use of these indices, combining three crucial variables (potency, MW and PSA) in a 2D graphical representation of chemical space, to perform a retrospective mapping of SAR data for a current TTR inhibitors database, and we propose prospective strategies to use these efficiency indices and chemico-biological space maps for optimization and drug design efforts for TTR ligands.
2012-05-14T06:53:48Z
2012-05-14T06:53:48Z
2011
comunicaciĆ³n de congreso
Molecular Informatics
1868-1743
http://hdl.handle.net/10261/49581
10.1002/minf.201000157
1868-1751
eng
http://dx.doi.org/10.1002/minf.201000157
closedAccess
Wiley-VCH