Activity cliffs in drug discovery: Dr Jekyll or Mr Hyde?

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

Maykel Cruz Monteagudo (Autor) Outra; Jose L Medina Francos (Autor) Outra; Yunierkis Perez Castillo (Autor) Outra; Orazio Nicolotti (Autor) Outra; Natalia N D S Cordeiro (Autor) FCUP; Fernanda Borges (Autor) FCUP

Revista

Título: Drug Discovery Today

Vol. 19

Páginas: 1069-1080

ISSN: 1359-6446

Editora: Elsevier

Indexação

ISI Web of Knowledge - 116 Citações

ISI Web of Science

Scopus - 125 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

CORDIS: Ciências Físicas > Química

Outras Informações

ID Authenticus: P-009-S5M

DOI: 10.1016/j.drudis.2014.02.003

Abstract (EN): The impact activity cliffs have on drug discovery is double-edged. For instance, whereas medicinal chemists can take advantage of regions in chemical space rich in activity cliffs, QSAR practitioners need to escape from such regions. The influence of activity cliffs in medicinal chemistry applications is extensively documented. However, the 'dark side' of activity cliffs (i.e. their detrimental effect on the development of predictive machine learning algorithms) has been understudied. Similarly, limited amounts of work have been devoted to propose potential solutions to the drawbacks of activity cliffs in similarity-based approaches. In this review, the duality of activity cliffs in medicinal chemistry and computational approaches is addressed, with emphasis on the rationale and potential solutions for handling the 'ugly face' of activity cliffs.

Idioma: Inglês

Tipo (Avaliação Docente): Científica