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.

journal_name

Drug Discov Today

journal_title

Drug discovery today

authors

Senger MR,Fraga CA,Dantas RF,Silva FP Jr

doi

10.1016/j.drudis.2016.02.004

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

868-72

issue

6

eissn

1359-6446

issn

1878-5832

pii

S1359-6446(16)30030-7

journal_volume

21

pub_type

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