Author | Dantas, Rafael Ferreira | |
Author | Evangelista, Tereza Cristina Santos | |
Author | Neves, Bruno Junior | |
Author | Senger, Mario Roberto | |
Author | Andrade, Carolina Horta | |
Author | Ferreira, Sabrina Baptista | |
Author | Silva Junior, Floriano Paes | |
Access date | 2020-08-08T20:59:08Z | |
Available date | 2020-08-08T20:59:08Z | |
Document date | 2019 | |
Citation | DANTAS, Rafael Ferreira et al. Dealing with frequent hitters in drug discovery: a multidisciplinary view on the issue of filtering compounds on biological screenings. Expert Opinion on Drug Discovery, p. 1-15, 2019. | pt_BR |
ISSN | 1746-0441 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/42603 | |
Language | eng | pt_BR |
Publisher | Taylor & Francis | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Descoberta de drogas | pt_BR |
Subject in Portuguese | Visão multidisciplinar | pt_BR |
Subject in Portuguese | Filtragem de compostos | pt_BR |
Subject in Portuguese | Exames biológicos | pt_BR |
Title | Dealing with frequent hitters in drug discovery: a multidisciplinary view on the issue of filtering compounds on biological screenings | pt_BR |
Type | Article | pt_BR |
DOI | 10.1080/17460441.2019.1654453 | |
Abstract | Introduction: The timely identification biologically active chemicals, in disease relevant screening
assays, is a major endeavor in drug discovery. The existence of frequent hitters (FHs) in non-related
assays poses a formidable challenge in terms of whether to consider these molecules as chemical gold
or promiscuous non-selective reactive trash (also known as PAINS – pan assay interference compounds).
Areas covered: In this review, the authors bring together expertize in synthetic chemistry, cheminformatics and biochemistry, three key areas for dealing with FHs. They discuss synthetic methods facilitating preparation of chemically diverse molecular libraries, while favoring activity in the biological
space. They also survey and discuss recent computational advances in the prediction of PAINS from
chemical structures. Finally, they review experimental approaches for the validation of the biological
activity of screening hits and discuss alternatives for exploiting promiscuity and chemical reactivity.
Expert opinion: It’s essential to develop more efficient computational methods to reliably recognize
PAINS in distinct molecular environments. Accordingly, advances in synthetic chemistry hold the
promise to provide a better quality of chemical matter for drug discovery. Medicinal chemists should
be more open to screening for hits showing biologically complex mechanisms of action rather than
discarding molecules that may prove valuable as innovative disease treatments. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Química. Laboratório de Síntese Orgânica e Prospecção Biológica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | UniEVANGÉLICA. Centro Universitário de Anápolis. Laboratório de Cheminformática. Anápolis, GO, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal de Goiás. Faculdade de Farmácia. LabMol - Laboratório para Modelagem Molecular e Design de Drogas. Goiânia, GO, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Química. Laboratório de Síntese Orgânica e Prospecção Biológica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Drug discovery | pt_BR |
Subject | Multidisciplinary view | pt_BR |
Subject | Filtering compounds | pt_BR |
Subject | Biological screenings | pt_BR |
e-ISSN | 1746-045X | |
Embargo date | 2022-01-01 | |