Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem. 2012 Mar 15;20(6):1902-9. doi: 10.1016/j.bmc.2011.11.070. Epub 2011 Dec 20.

Identification and validation of protein targets of bioactive small molecules.

Author information

1
Department of Pharmacology, Johns Hopkins University School of Medicine, MD, USA.

Abstract

Identification and validation of protein targets of bioactive small molecules is an important problem in chemical biology and drug discovery. Currently, no single method is satisfactory for this task. Here, we provide an overview of common methods for target identification and validation that historically were most successful. We have classified for the first time the existing methods into two distinct and complementary types, the 'top-down' and 'bottom-up' approaches. In a typical top-down approach, the cellular phenotype is used as a starting point and the molecular target is approached through systematic narrowing down of possibilities by taking advantage of the detailed existing knowledge of cellular pathways and processes. In contrast, the bottom-up approach entails the direct detection and identification of the molecular targets using affinity-based or genetic methods. A special emphasis is placed on target validation, including correlation analysis and genetic methods, as this area is often ignored despite its importance.

PMID:
22226983
PMCID:
PMC3714012
DOI:
10.1016/j.bmc.2011.11.070
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center