Compound annotation with real time cellular activity profiles to improve drug discovery

ABSTRACT

Introduction: In the past decade, a range of innovative strategies have been developed to improve the productivity of pharmaceutical research and development. In particular, compound annotation, combined with informatics, has provided unprecedented opportunities for drug discovery.

Areas covered: In this review, a literature search from 2000 to 2015 was conducted to provide an overview of the compound annotation approaches currently used in drug discovery. Based on this, a framework related to a compound annotation approach using real-time cellular activity profiles for probe, drug, and biology discovery is proposed.

Expert opinion: Compound annotation with chemical structure, drug-like properties, bioactivities, genome-wide effects, clinical phenotypes, and textural abstracts has received significant attention in early drug discovery. However, these annotations are mostly associated with endpoint results. Advances in assay techniques have made it possible to obtain real-time cellular activity profiles of drug molecules under different phenotypes, so it is possible to generate compound annotation with real-time cellular activity profiles. Combining compound annotation with informatics, such as similarity analysis, presents a good opportunity to improve the rate of discovery of novel drugs and probes, and enhance our understanding of the underlying biology.

KEYWORDS:

• Annotation
• drug discovery
• real-time cellular activity profile
• ontology

Article highlights.

• Compound annotation, combining with informatics, has been increasingly used in discovering new biology, drugs, and probe molecules.

• Current compounds in public databases are annotated with chemical structure, drug-like properties, bioactivity data, clinical phenotypes, genome wide effects, and textual abstracts.

• However, current compound annotation approaches are mostly associated with endpoint results. Thus, informatics-based analysis of these annotations only predicts the potential of drug-target interactions and generates biology hypotheses.

• Label-free cell phenotypic techniques have come of age, so real-time compound annotation is possible.

• Now, it is time to call for the development of label-free bioassay ontology and standardization of real-time compound annotation approach.

• Real-time compound annotation, although limited in literature reports, holds great potential in accelerating biology, probe, and drug discovery.This box summarizes key points contained in the article.

Financial and Competing Interests Disclosure

Ye Fang is a research director and fellow in the Science and Technology Division of Corning Incorporated. He is also a stockholder of Corning Inc. He has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.