title: Filtering promiscuous compounds in early drug discovery: is it a good idea?
abstract: The use of computational filters for excluding supposedly nonspecific and promiscuous compounds from chemical libraries is a controversial issue, because many drugs used in clinics today would never reach the market if these filters were applied. In part, this conflict could be caused by the paradigm: one-drug-one-target, even though it is widely agreed that drug action is a result of a complex network of biomolecular interactions. Therefore, the so-called pan assay interference compounds (PAINS) or promiscuous compounds could be in fact assay artifacts, false positives or, simply, bright chemical matter (BCM) composed of privileged scaffolds, as we propose here. Despite apparent promiscuity, BCM can be tailored into new and safe drugs after overcoming selectivity criteria.
authors.affiliation: Laboratório de Bioquímica Experimental e Computacional de Fármacos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. Electronic address: mario.senger@ioc.fiocruz.br.
authors.forename: Mario R
authors.initials: MR
authors.lastname: Senger
authors.affiliation: Laboratório de Avaliação e Síntese de Substâncias Bioativas, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
authors.affiliation: Laboratório de Bioquímica Experimental e Computacional de Fármacos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Rafael F
authors.initials: RF
authors.lastname: Dantas
authors.affiliation: Laboratório de Bioquímica Experimental e Computacional de Fármacos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. Electronic address: floriano@ioc.fiocruz.br.
authors.forename: Floriano P
authors.initials: FP
authors.lastname: Silva
mesh_terms: D001681:Biological Assay; D055808:Drug Discovery; D054852:Small Molecule Libraries
chemical_list: D054852:Small Molecule Libraries