In silico directed chemical probing of the adenosine receptor family.

Abstract:

:One of the grand challenges in chemical biology is identifying a small-molecule modulator for each individual function of all human proteins. Instead of targeting one protein at a time, an efficient approach to address this challenge is to target entire protein families by taking advantage of the relatively high levels of chemical promiscuity observed within certain boundaries of sequence phylogeny. We recently developed a computational approach to identifying the potential protein targets of compounds based on their similarity to known bioactive molecules for almost 700 targets. Here, we describe the direct identification of novel antagonists for all four adenosine receptor subtypes by applying our virtual profiling approach to a unique synthesis-driven chemical collection composed of 482 biologically-orphan molecules. These results illustrate the potential role of in silico target profiling to guide efficiently screening campaigns directed to discover new chemical probes for all members of a protein family.

journal_name

Bioorg Med Chem

authors

Areias FM,Brea J,Gregori-Puigjané E,Zaki ME,Carvalho MA,Domínguez E,Gutiérrez-de-Terán H,Proença MF,Loza MI,Mestres J

doi

10.1016/j.bmc.2010.03.048

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

3043-52

issue

9

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(10)00252-X

journal_volume

18

pub_type

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